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| Fetal anomalies v1.204 | AL117258.1 |
Ain Roesley gene: AL117258.1 was added gene: AL117258.1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AL117258.1 were set to 34903892 Phenotypes for gene: AL117258.1 were set to Heterotaxy; congenital heart defects Review for gene: AL117258.1 was set to GREEN gene: AL117258.1 was marked as current diagnostic Added comment: Gene also known as CIROP and LMLN2 Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy. Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers. Sources: Literature Sources: Literature |
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| Fetal anomalies v1.197 | THSD1 |
Zornitza Stark gene: THSD1 was added gene: THSD1 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: THSD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: THSD1 were set to 33569873; 27895300 Phenotypes for gene: THSD1 were set to Lymphatic malformation 13, MIM# 620244 Review for gene: THSD1 was set to GREEN Added comment: PMID: 33569873 - 1 fetus with a homozygous PTC and nonimmune hydrops fetalis (NIHF), congenital heart disease and hemangiomas. FHx of 1/3 triplets with severe hydrops fetalis, not sequenced. - Paper reviews previous NIHF cases and reports another homozygous PTC in two families ( and a recurring homozygous missense (p.Cys206Tyr) in three families. PMID: 27895300- Mouse model has hydrocephaly with poor perfusion. Sources: Expert Review |
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| Fetal anomalies v1.131 | SENP7 |
Elena Savva gene: SENP7 was added gene: SENP7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SENP7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SENP7 were set to PMID: 37460201 Phenotypes for gene: SENP7 were set to Arthrogryposis multiplex congenita, MONDO:0015168, SENP7-related Review for gene: SENP7 was set to AMBER Added comment: PMID: 37460201 - 1 family (4 affecteds, sibling pair and 1st cousin) with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia. Fetus could not be tested, so 3 confirmed genetically. - Homozygous for a PTC, decreased mRNA from one sample supports an NMD outcome. - Additional studies performed supporting downstream proteins expression being affected - Neutropenia observed in 2/3 patients Sources: Literature |
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| Fetal anomalies v1.114 | RAB34 |
Sarah Pantaleo gene: RAB34 was added gene: RAB34 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RAB34 were set to PMID: 37384395 Phenotypes for gene: RAB34 were set to Clefting; corpus callosum; short bones; hypertelorism; polydactyly; cardiac defects; anorectal anomalies Penetrance for gene: RAB34 were set to Complete Review for gene: RAB34 was set to GREEN Added comment: Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogenous disorders characterised by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in >20 genes encoding ciliary proteins have been found to cause OFDS. Identified by WES biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families (aided by GeneMatcher). Affected individuals presented a novel form of OFDS accompanied by cardiac, cerebral, skeletal (eg. Shortening of long bones), and anorectal defects. RAB34 encodes a member of the Lab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Protein products of pathogenic variants clustered near the RAB34 C-terminus exhibit a strong loss of function. Onset is prenatal (multiple developmental defects including short femur, polydactyly, heart malformations, kidney malformations, brain malformations), resulting in medical termination for three probands. In the fourth, the only one alive at birth, proband born at 39+5 weeks, normal growth parameters after pregnancy with polyhydramnios, corpus callosum agenesis and polydactyly. Respiratory distress at birth. All four probands presented typical features of ciliopathy disorders, overlapping with oral, facial and digital abnormalities. All with homozygous missense variants. All absent in gnomAD (in homozygous state). Sanger sequencing confirmed mode of inheritance. Sources: Literature |
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| Fetal anomalies v1.39 | PAN2 |
Naomi Baker gene: PAN2 was added gene: PAN2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAN2 were set to PMID:35304602; 29620724 Phenotypes for gene: PAN2 were set to Syndromic disease MONDO:0002254 Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck. PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system. Sources: Literature |
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| Fetal anomalies v1.11 | NEXN |
Krithika Murali gene: NEXN was added gene: NEXN was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NEXN was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: NEXN were set to 33947203; 33949776; 35166435; 32058062 Phenotypes for gene: NEXN were set to Lethal fetal cardiomyopathy; Hydrops fetalis; Cardiomyopathy, dilated 1CC - MIM#613122 Review for gene: NEXN was set to GREEN Added comment: NEXN encodes cardiac Z-disc protein. Monoallelic variants associated with both paediatric and adult-onset dilated cardiomyopathy. 3 unrelated families reported with biallelic variants associated with lethal fetal cardiomyopathy. PMID 35166435 - 3 consecutive affected pregnancies with intrauterine fetal death, dilated cardiomyopathy +/- fetal hydrops/IUGR. Autopsy findings of DCM, endomyocardial fibroelastosis. Non-consanguineous Swedish family. Homozygous variant identified - (NM_144573:c.1302del;p.(Ile435Serfs*3)). Heterozygous carriers enriched in Swedish population. PMID: 33949776 - Report a 11 year old with mild DCM on cardiac MRI with a heterozygous paternally inherited variant (1949_1951del), father also had mild DCM. Also report a 2nd patient who presented with fetal Hydrops at 33 weeks gestation requiring emergency C-section. Homozygous c.1174C > T,p.(R392*) variants identified. Microscopic investigation showed endomyocardial fibroelastosis. PMID: 32058062 - male fetus, compound het, DCM, MTOP; previous pregnancy with the same history. Sources: Literature |
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| Fetal anomalies v0.4699 | NCAPD2 |
Zornitza Stark gene: NCAPD2 was added gene: NCAPD2 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: NCAPD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NCAPD2 were set to 31056748; 27737959; 28097321 Phenotypes for gene: NCAPD2 were set to Microcephaly 21, primary, autosomal recessive; OMIM #617983 Review for gene: NCAPD2 was set to GREEN Added comment: Three families reported: 1 family with 2 sibs with microcephaly and ID, and homozygous NCAPD2 mutation, which segregated with disease. No functional evidence. 1 family with 1 affected and homozygous NCAPD2 mutation, which segregated with disease. Patient fibroblasts showed impaired chromosome segregation and abnormal recovery from mitotic condensation compared to controls. 1 family with 2 sibs with microcephaly, growth retardation, and ID, and homozygous NCAPD2 mutation, which segregated with disease. Functional studies of the variants and studies of patient cells were not performed. IUGR reported. Sources: Expert Review |
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| Fetal anomalies v0.4478 | MCM7 |
Krithika Murali gene: MCM7 was added gene: MCM7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCM7 were set to 33654309; 34059554 Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency Review for gene: MCM7 was set to AMBER Added comment: Association with congenital microcephaly. No new publications since last PanelApp review --- MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present. ------ Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families. - PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment. Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression. - PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7. Sources: Literature |
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| Fetal anomalies v0.4443 | ROGDI |
Zornitza Stark changed review comment from: Kohlschutter-Tonz syndrome (KTZS) is an autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discolouration of the teeth. More than 10 families reported.; to: Kohlschutter-Tonz syndrome (KTZS) is an autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discolouration of the teeth. More than 10 families reported. Cerebellar hypoplasia and ventriculomegaly described. |
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| Fetal anomalies v0.4386 | SLC10A7 | Zornitza Stark Phenotypes for gene: SLC10A7 were changed from Chondrodysplasia with multiple dislocations and amelogenesis imperfecta to Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis, MIM# 618363 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4383 | SLC13A5 | Zornitza Stark Phenotypes for gene: SLC13A5 were changed from EPILEPTIC ENCEPHALOPATHY WITH SEIZURE ONSET IN THE FIRST DAYS OF LIFE to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905; MONDO:0014392 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4317 | TUBGCP2 |
Chirag Patel gene: TUBGCP2 was added gene: TUBGCP2 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TUBGCP2 were set to PMID: 31630790 Phenotypes for gene: TUBGCP2 were set to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM # 618737 Review for gene: TUBGCP2 was set to GREEN Added comment: Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures (PAMDDFS) is an autosomal recessive neurologic disorder characterized by progressive microcephaly associated with abnormal facial features, hypotonia, and variable global developmental delay with impaired intellectual development. Brain imaging shows variable malformation of cortical development on the lissencephaly spectrum, mainly pachygyria and thin corpus callosum. 4 unrelated patients with homozygous or compound heterozygous mutations in the TUBGCP2 gene, found by WES and segregated with the disorder in all families. Functional studies of the variants were not performed, but analysis of patient fibroblasts derived from the patient with a splice site mutation demonstrated the production of several abnormal transcripts that were predicted to result in a loss of function. Sources: Expert list |
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| Fetal anomalies v0.4305 | VPS50 |
Chirag Patel gene: VPS50 was added gene: VPS50 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS50 were set to PMID: 34037727 Phenotypes for gene: VPS50 were set to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685 Review for gene: VPS50 was set to AMBER Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants. Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)). VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor. As discussed by Schneeberger et al (refs provided in text): - VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development. - Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality. Studies performed by Schneeberger et al included: - Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del). - Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels. - Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts. - Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function. As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders". There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes. Sources: Expert list |
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| Fetal anomalies v0.4273 | ENO1 |
Daniel Flanagan gene: ENO1 was added gene: ENO1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: ENO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ENO1 were set to 32488097 Phenotypes for gene: ENO1 were set to Polymicrogyria; microcephaly Review for gene: ENO1 was set to RED Added comment: ENO1 identified as a polymicrogyria candidate gene from the smallest case of 1p36 duplication reported to date, in a 35yo F (onset at 8mo) presenting intellectual disability, microcephaly, epilepsy and perisylvian polymicrogyria. The duplication only encompassed 2 genes, ENO1 and RERE, and gene expression analysis performed using the patient cells revealed reduced expression, mimicking haploinsufficiency. Eno1 inactivation in rats was shown to cause a brain development defect. According to OMIM, ENO1 is deleted in glioblastoma, which is tolerated by the expression of ENO2. Sources: Expert list |
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| Fetal anomalies v0.4180 | MIA3 |
Chirag Patel gene: MIA3 was added gene: MIA3 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIA3 were set to PMID: 32101163, 33778321 Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269 Review for gene: MIA3 was set to AMBER Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported, homozygous variant affecting splicing. Mouse model has absence of bone mineralization. Can present with IUGR antenatally. Suitable for fetal anomalies panel. Sources: Expert list |
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| Fetal anomalies v0.2928 | SP7 | Zornitza Stark reviewed gene: SP7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type XII, MIM# 613849; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2862 | SEC24D | Zornitza Stark Phenotypes for gene: SEC24D were changed from SYNDROMIC OSTEOGENESIS IMPERFECTA to Cole-Carpenter syndrome 2, MIM# 616294 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2756 | ERGIC1 |
Krithika Murali gene: ERGIC1 was added gene: ERGIC1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ERGIC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERGIC1 were set to 28317099; 34037256; 31230720 Phenotypes for gene: ERGIC1 were set to Arthrogryposis multiplex congenita 2, neurogenic type; OMIM # 208100 Review for gene: ERGIC1 was set to GREEN Added comment: Recent Panelapp review by Z. Stark Oct 2021 - no new publications since --- Pehlivan et al. 2019 (PMID:31230720) identified the third case of arthrogryposis in a child who harboured a previously unreported homozygous variant (c.782G>A; p.Gly261Asp) in this gene. Parents were heterozygous carriers. Functional studies were not performed. Created: 14 Oct 2021, 7:23 a.m. | Last Modified: 14 Oct 2021, 7:23 a.m. Panel Version: 0.9373 Reinstein et al. (2018) used WES in a large consanguineous Israeli Arab kindred consisting of 16 patients affected with the neurogenic type of arthrogryposis multiplex congenita. They identified a homozygous missense (V98E) mutation in ERGIC1 gene, which segregated with the disorder in the kindred, and was not found in the ExAC database or in 212 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi. Marconi et al (2021) used genome sequencing in a consanguineous family with 2 affected siblings presenting congenital arthrogryposis and some facial dysmorphism. They identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents. Sources: Literature Sources: Literature |
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| Fetal anomalies v0.2728 | SHMT2 |
Krithika Murali gene: SHMT2 was added gene: SHMT2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SHMT2 were set to 33015733 Phenotypes for gene: SHMT2 were set to Polymicrogyria; corpus callosum anomalies; Microcephaly; Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities - #619121 Review for gene: SHMT2 was set to GREEN Added comment: Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities particularly thin corpus callosum and polymicrogyria (NEDCASB) associated with biallelic SHMT2 variants. Antenatal detection of microcephaly reported. -- Detailed PanelApp review Oct 2020 - no new evidence to add García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants. All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs. Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones. SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF. Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes. While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction. Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect. The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity). Sources: Literature |
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| Fetal anomalies v0.2695 | IFITM5 | Zornitza Stark Phenotypes for gene: IFITM5 were changed from OSTEOGENESIS IMPERFECTA TYPE V to Osteogenesis imperfecta, type V MIM#610967 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2554 | SERPINH1 | Zornitza Stark reviewed gene: SERPINH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20188343; Phenotypes: Osteogenesis imperfecta, type X, MIM# 613848; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2479 | ZMYND11 |
Zornitza Stark changed review comment from: New case series of additional 16 individuals reported, including four individuals from the same family. Common phenotypic features: developmental delay, particularly affecting speech, mild‐moderate intellectual disability, significant behavioral abnormalities, seizures, and hypotonia. There are subtle shared dysmorphic features, including prominent eyelashes and eyebrows, a depressed nasal bridge with bulbous nasal tip, anteverted nares, thin vermilion of the upper lip, and wide mouth. Novel features include brachydactyly and tooth enamel hypoplasia. Most identified variants are likely to result in premature truncation and/or nonsense‐mediated decay. Two ZMYND11 variants located in the final exon reported —p.(Gln586*) (likely escaping nonsense‐mediated decay) and p.(Cys574Arg)—are predicted to disrupt the MYND‐type zinc‐finger motif and likely interfere with binding to its interaction partners.; to: New case series of additional 16 individuals reported, including four individuals from the same family. Common phenotypic features: developmental delay, particularly affecting speech, mild‐moderate intellectual disability, significant behavioral abnormalities, seizures, and hypotonia. There are subtle shared dysmorphic features, including prominent eyelashes and eyebrows, a depressed nasal bridge with bulbous nasal tip, anteverted nares, thin vermilion of the upper lip, and wide mouth. Novel features include brachydactyly and tooth enamel hypoplasia. Most identified variants are likely to result in premature truncation and/or nonsense‐mediated decay. Two ZMYND11 variants located in the final exon reported —p.(Gln586*) (likely escaping nonsense‐mediated decay) and p.(Cys574Arg)—are predicted to disrupt the MYND‐type zinc‐finger motif and likely interfere with binding to its interaction partners. Presentation is post-natal. |
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| Fetal anomalies v0.2366 | FKBP10 | Belinda Chong reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20696291, 20362275, 20839288, 21567934, 21567934, 23712425, 22718341; Phenotypes: Bruck syndrome 1 MIM#259450, Osteogenesis imperfecta, type XI MIM#610968; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2366 | FAM46A |
Belinda Chong changed review comment from: Comment when marking as ready: HGNC approved name: TENT5A Osteogenesis imperfecta type XVIII (OI18) is characterized by congenital bowing of the long bones, wormian bones, blue sclerae, vertebral collapse, and multiple fractures in the first years of life. In 4 children from 3 unrelated consanguineous families with osteogenesis imperfecta, Doyard et al. (2018) identified homozygosity for mutations in the FAM46A gene. The mutations were identified by exome sequencing and confirmed by Sanger sequencing.; to: Comment when marking as ready: HGNC approved name: TENT5A Osteogenesis imperfecta type XVIII (OI18) is characterized by congenital bowing of the long bones, wormian bones, blue sclerae, vertebral collapse, and multiple fractures in the first years of life. In 4 children from 3 unrelated consanguineous families with osteogenesis imperfecta, Doyard et al. (2018) identified homozygosity for mutations in the FAM46A gene. The mutations were identified by exome sequencing and confirmed by Sanger sequencing. |
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| Fetal anomalies v0.2366 | FAM46A | Belinda Chong reviewed gene: FAM46A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type XVIII MIM#617952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2320 | FOXH1 |
Krithika Murali edited their review of gene: FOXH1: Added comment: No OMIM gene disease association. Overall, evidence for this gene and its association with congenital heart disease is conflicting. Roessler et al 2008 PMID 18538293 Pilot consortium study of 375 unrelated individuals prospectively ascertained with cardiovascular malformations. Patients not seen at NIH and parents/siblings not consented. Therefore only samples from proband collected. Also screened 300-500 patients with holoprosencephaly and 125 unrelated controls. Over 60 heterozygous FOXH1 variants reported in patients with congenital heart disease or holoprosencephaly. The majority of reported variants were of questionable pathogenicity as they were present in gnomad, had variants present in gnomad with alternative amino acid changes at the same position, had limited evidence of effect on FOXH1 functional activity or were synonymous variants. Furthermore, no variant segregation data available. De Luca et al 2009 PMID 19933292 FOXH1 (Pro21Ser) missense variant identified. Not present in gnomad but in area of low coverage, alternative aa change reported in the same location in x1 het. Identified in proband with TGA and x2 other unaffected family members. Proband who was also heterozogous for an amino acid substitution (Gly17Cys) in the ZIC3 gene Wei et al 2020 Clinical Genetics PMID 32003456 Exome sequencing performed in 605 patients with sporadic conotruncal defects and 300 controls in patients of Chinese descent with ages ranging from 6 days to 12 years old, majority <2 years old. 14 gene panel used. Identified 7 FOXH1 missense variants in 10 unrelated patients with congenital heart disease. All reported variants associated with reduced protein expression of FOXH1 protein on Western blot to varying degrees. No segregation data provided. • FOXH1 c.104C>G p.P35R identified in a 9 month old with double outlet right ventricle. Absent from gnomad but is in an area of low exome coverage. Variant with alternative amino acid change at same position (FOXH1 c.104C>T p.P35L) previously identified in a patient with congenital heart disease (Roessler et al 2008) • X2 patients - FOXH1 c.205T>C p.Phe69Leu. Also present in gnomad – x1 het non-Finnish European. X1 patient with alternative amino acid change at same position also identified (FOXH1 c.206T>C p.Phe69Ser) – absent from gnomad. • X2 patients with FOXH1 c.209T>C p.Phe70Ser - absent from gnomad • X2 patients with FOXH1 c.232A>G p.Lys78Glu – x2 hets gnomad (European non-Finnish, South Asian) • X1 patient with FOXH1 c.277A>G p.Lys93Glu – x1 het gnomad (European Finnish) • X1 patients FOXH1 c.277A>G p.Glu165Gln – absent from gnomad, benign in silicos PMID 12094232, PMID 16304598 - Previous mouse models have demonstrated a role for Foxh1 in heart morphogenesis.; Changed rating: AMBER; Changed publications: 18538293, 19933292, 32003456, 12094232, 16304598; Changed phenotypes: Congenital heart disease |
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| Fetal anomalies v0.2300 | DNM1 |
Zornitza Stark changed review comment from: Well-established link between heterozygous variants in DNM1 and developmental and epileptic encephalopathy. Yigit et al. 2021 (PMID: 34172529) recently reported two unrelated patients with DEE and homozygous truncating variants (c.97C>T; p.(Gln33*) and c.850C>T; p.(Gln284*), respectively) in the DNM1 gene. All parents were heterozygous carriers but did not show any clinical symptoms indicating a recessive inheritance pattern. No function studies were performed.; to: Well-established link between heterozygous variants in DNM1 and developmental and epileptic encephalopathy. Yigit et al. 2021 (PMID: 34172529) recently reported two unrelated patients with DEE and homozygous truncating variants (c.97C>T; p.(Gln33*) and c.850C>T; p.(Gln284*), respectively) in the DNM1 gene. All parents were heterozygous carriers but did not show any clinical symptoms indicating a recessive inheritance pattern. No function studies were performed. Clinical presentation is typically post-natal. |
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| Fetal anomalies v0.2187 | TMEM38B | Chirag Patel reviewed gene: TMEM38B: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 23316006, 23054245, 26911354, 34902613; Phenotypes: Osteogenesis imperfecta, type XIV , OMIM #615066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1929 | GNAS | Zornitza Stark Phenotypes for gene: GNAS were changed from ALBRIGHT HEREDITARY OSTEODYSTROPHY; GNAS HYPERFUNCTION; PSEUDOHYPOPARATHYROIDISM TYPE 1B; ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA to Pseudohypoparathyroidism Ia, MIM# 103580 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1820 | FTL | Zornitza Stark Phenotypes for gene: FTL were changed from HEREDITARY HYPERFERRITINEMIA-CATARACT SYNDROME to Hyperferritinemia-cataract syndrome, MIM# 600886 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1818 | FTL | Zornitza Stark edited their review of gene: FTL: Added comment: Cataracts are congenital in some and may be detectable antenatally.; Changed rating: GREEN; Changed phenotypes: Hyperferritinemia-cataract syndrome, MIM# 600886; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1682 | CCDC65 |
Zornitza Stark changed review comment from: Same homozygous PTC (p.I293Pfs*2) reported in 3 Ashkenzi Jewish families. PMID: 24094744 performs functional assay on null zebrafish model - replicates human phenotype supporting LOF. Three different LoF reported in context of primary ciliary dyskinesia by diagnostic laboratories in ClinVar.; to: Same homozygous PTC (p.I293Pfs*2) reported in 3 Ashkenzi Jewish families. PMID: 24094744 performs functional assay on null zebrafish model - replicates human phenotype supporting LOF. Three different LoF reported in context of primary ciliary dyskinesia by diagnostic laboratories in ClinVar. Situs inversus not reported. |
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| Fetal anomalies v0.1514 | FAM20A | Zornitza Stark Phenotypes for gene: FAM20A were changed from AMELOGENESIS IMPERFECTA AND GINGIVAL FIBROMATOSIS SYNDROME to Amelogenesis imperfecta, type IG (enamel-renal syndrome) 204690 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1469 | FAM20A | Belinda Chong reviewed gene: FAM20A: Rating: RED; Mode of pathogenicity: None; Publications: 23468644, 18597613, 21549343, 21990045; Phenotypes: Amelogenesis imperfecta, type IG (enamel-renal syndrome) 204690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1411 | CREB3L1 | Zornitza Stark reviewed gene: CREB3L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24079343, 28817112, 29936144, 30657919; Phenotypes: Osteogenesis imperfecta, type XVI, 616229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1322 | ERF | Zornitza Stark Marked gene: ERF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1322 | ERF | Zornitza Stark Gene: erf has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1322 | ERF | Zornitza Stark Phenotypes for gene: ERF were changed from Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia; COMPLEX CRANIOSYNOSTOSIS to Chitayat syndrome, MIM#617180; Craniosynostosis 4, MIM#600775 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1321 | ERF | Zornitza Stark Publications for gene: ERF were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1320 | ERF | Zornitza Stark Mode of inheritance for gene: ERF was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1319 | ERF |
Zornitza Stark changed review comment from: ID is not really part of the phenotype of either condition; mild learning difficulties described in some individuals affected by craniosynostosis 4.; to: Over 20 unrelated families reported. Craniosynostosis-4 includes lambdoid, sagittal, metopic, coronal, and multisuture forms. The overall prevalence of ERF mutations in patients with syndromic craniosynostosis is around 2%, and 0.7% in clinically nonsyndromic craniosynostosis. Variants in this gene are also associated with Chitayat syndrome, which has skeletal abnormalities as a feature. |
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| Fetal anomalies v0.1319 | ERF | Zornitza Stark edited their review of gene: ERF: Changed rating: GREEN; Changed publications: 23354439, 26097063, 32370745, 30758909 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1104 | B9D1 | Zornitza Stark changed review comment from: PMID: 24886560 - 2 unrelated patients with mild Joubert syndrome patients found (1 hom missense, 1 chet inframe deletion/missense). Authors suggest biallelic null variants are lethal. PMID: 21493627 - 1 fetus with Meckell syndrome and chet for a splice/gene deletion. The splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. Authors perform functional studies on patient cells but given the large deletion/CEP290 variant i dont see the results are usable PMID: 25920555 - another report of digenic inheritance - not usable, patient was only heterozygous for a single B9D1 variant Summary: 2 unrelated patients, AMBER; to: PMID: 24886560 - 2 unrelated patients with mild Joubert syndrome patients found (1 hom missense, 1 chet inframe deletion/missense). Authors suggest biallelic null variants are lethal. PMID: 21493627 - 1 fetus with Meckell syndrome and chet for a splice/gene deletion. The splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.886 | PLS3 |
Krithika Murali gene: PLS3 was added gene: PLS3 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: PLS3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: PLS3 were set to 32655496; 25209159; 29736964; 29884797; 28777485; 24088043 Phenotypes for gene: PLS3 were set to Bone mineral density QTL18, osteoporosis - MIM#300910 Review for gene: PLS3 was set to AMBER Added comment: First reported in 2013 (PMID 24088043). Associated with childhood-onset primary osteoporosis with presentations of varying severity with a phenotype similar to osteogenesis imperfecta. No published reports of antenatal diagnosis. Sources: Expert list, Literature |
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| Fetal anomalies v0.739 | PPIB | Zornitza Stark Phenotypes for gene: PPIB were changed from Osteogenesis imperfecta, type IX 259440 to Osteogenesis imperfecta, type IX, MIM# 259440 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.737 | PPIB | Naomi Baker reviewed gene: PPIB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19781681, 32392875; Phenotypes: Osteogenesis imperfecta, type IX, MIM# 259440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.693 | CRTAP | Zornitza Stark Phenotypes for gene: CRTAP were changed from Osteogenesis imperfecta, type VII 610682 to Osteogenesis imperfecta, type VII, MIM# 610682 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.614 | MBTPS2 | Zornitza Stark Phenotypes for gene: MBTPS2 were changed from IFAP syndrome with or without BRESHECK syndrome 308205; Keratosis follicularis spinulosa decalvans, X-linked 308800 to IFAP syndrome with or without BRESHECK syndrome MIM#308205; Osteogenesis imperfecta, type XIX, MIM#301014 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.582 | MBTPS2 | Daniel Flanagan reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27380894, 19361614, 21426410; Phenotypes: Osteogenesis imperfecta, type XIX, (MIM301014), IFAP syndrome with or without BRESHECK syndrome (MIM#308205), Keratosis follicularis spinulosa decalvans, X-linked (MIM#308800), ?Olmsted syndrome, X-linked (MIM#300918); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.572 | COL1A2 | Zornitza Stark Phenotypes for gene: COL1A2 were changed from Osteogenesis imperfecta; Ehlers-Danlos syndrome to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120; Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821; Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320; Osteogenesis imperfecta, type II, MIM# 166210; Osteogenesis imperfecta, type III, MIM# 259420; Osteogenesis imperfecta, type IV, MIM# 166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.571 | COL1A2 | Zornitza Stark edited their review of gene: COL1A2: Added comment: Well established gene-disease associations, likely representing a spectrum. The more severe phenotypes can present antenatally particularly with skeletal features.; Changed rating: GREEN; Changed phenotypes: Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, MIM# 619120, Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821, Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320, Osteogenesis imperfecta, type II, MIM# 166210, Osteogenesis imperfecta, type III, MIM# 259420, Osteogenesis imperfecta, type IV, MIM# 166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.571 | COL1A1 | Zornitza Stark Phenotypes for gene: COL1A1 were changed from OSTEOGENESIS IMPERFECTA TYPE III; CAFFEY DISEASE; OSTEOGENESIS IMPERFECTA TYPE I; OSTEOGENESIS IMPERFECTA TYPE IIA; EHLERS-DANLOS SYNDROME TYPE VIIA; COL1A1/2-RELATED OSTEOGENESIS IMPERFECTA; EHLERS-DANLOS SYNDROME, CLASSIC TYPE, COL1A1-RELATED to Caffey disease, MIM#114000; Ehlers-Danlos syndrome, arthrochalasia type, 1, MIM#130060; Osteogenesis imperfecta, type I, MIM#166200; Osteogenesis imperfecta, type II, MIM#166210; Osteogenesis imperfecta, type III, MIM#259420; Osteogenesis imperfecta, type IV, MIM#166220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.498 | P3H1 | Zornitza Stark Phenotypes for gene: P3H1 were changed from OSTEOGENESIS IMPERFECTA, TYPE VIII to Osteogenesis imperfecta, type VIII 610915 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.482 | P3H1 | Dean Phelan reviewed gene: P3H1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27864101, 33737016, 17277775, 19088120; Phenotypes: Osteogenesis imperfecta; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.453 | LTBP3 | Zornitza Stark Phenotypes for gene: LTBP3 were changed from PLATYSPONDYLY WITH AMELOGENESIS IMPERFECTA to Dental anomalies and short stature, MIM# 601216; Geleophysic dysplasia 3, MIM# 617809; Thoracic aneurysm | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.448 | IFITM5 | Ain Roesley reviewed gene: IFITM5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22863190, 22863195, 32383316, 24519609; Phenotypes: Osteogenesis imperfecta, type V MIM#610967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.324 | BMP1 | Zornitza Stark Phenotypes for gene: BMP1 were changed from Osteogenesis imperfecta type XIII 614856 to Osteogenesis imperfecta, type XIII , MIM#614856 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.322 | BMP1 | Zornitza Stark reviewed gene: BMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25402547, 22052668, 22482805, 25214535; Phenotypes: Osteogenesis imperfecta, type XIII , MIM#614856; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.101 | ADAR | Zornitza Stark Phenotypes for gene: ADAR were changed from AICARDI-GOUTIERES SYNDROME ASSOCIATED WITH A TYPE I INTERFERON SIGNATURE; DYSCHROMATOSIS SYMMETRICA HEREDITARIA 1 to Aicardi-Goutieres syndrome 6, MIM# 615010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | DSPP |
Zornitza Stark gene: DSPP was added gene: DSPP was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: DSPP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: DSPP were set to DENTINOGENESIS IMPERFECTA, SHIELDS TYPE II; DEAFNESS AUTOSOMAL DOMINANT TYPE 39 WITH DENTINOGENESIS IMPERFECTA 1 |
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| Fetal anomalies v0.0 | C4orf26 |
Zornitza Stark gene: C4orf26 was added gene: C4orf26 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: C4orf26 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C4orf26 were set to 22901946 Phenotypes for gene: C4orf26 were set to Amelogenesis imperfecta, type IIA4, 614832 |
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| Fetal anomalies v0.0 | TMEM38B |
Zornitza Stark gene: TMEM38B was added gene: TMEM38B was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: TMEM38B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM38B were set to 23054245; 23316006 Phenotypes for gene: TMEM38B were set to Osteogenesis imperfecta, type XIV, OMIM:615066; Osteogenesis imperfecta type 14, MONDO:0014029 |
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| Fetal anomalies v0.0 | SPARC |
Zornitza Stark gene: SPARC was added gene: SPARC was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SPARC was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SPARC were set to Osteogenesis imperfecta, type XVII, OMIM:616507; Osteogenesis imperfecta type 17, MONDO:0014672 |
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| Fetal anomalies v0.0 | SP7 |
Zornitza Stark gene: SP7 was added gene: SP7 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SP7 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SP7 were set to Osteogenesis imperfecta type 12, MONDO:0013460; Osteogenesis imperfecta, type XII, OMIM:613849 |
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| Fetal anomalies v0.0 | SLC24A4 |
Zornitza Stark gene: SLC24A4 was added gene: SLC24A4 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SLC24A4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC24A4 were set to AMELOGENESIS IMPERFECTA. |
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| Fetal anomalies v0.0 | SERPINH1 |
Zornitza Stark gene: SERPINH1 was added gene: SERPINH1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SERPINH1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SERPINH1 were set to Osteogenesis imperfecta type 10, MONDO:0013459; Osteogenesis imperfecta, type X, OMIM:613848 |
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| Fetal anomalies v0.0 | SERPINF1 |
Zornitza Stark gene: SERPINF1 was added gene: SERPINF1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SERPINF1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SERPINF1 were set to Osteogenesis imperfecta, type VI, OMIM:613982; Osteogenesis imperfecta type 6, MONDO:0013515 |
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| Fetal anomalies v0.0 | SEC24D |
Zornitza Stark gene: SEC24D was added gene: SEC24D was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: SEC24D was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SEC24D were set to SYNDROMIC OSTEOGENESIS IMPERFECTA |
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| Fetal anomalies v0.0 | MESD |
Zornitza Stark gene: MESD was added gene: MESD was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MESD were set to 31564437 Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX, OMIM:618644; Osteogenesis imperfecta, type 20, MONDO:0032846 |
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| Fetal anomalies v0.0 | FKBP10 |
Zornitza Stark gene: FKBP10 was added gene: FKBP10 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: FKBP10 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FKBP10 were set to Bruck syndrome 1, MONDO:0009806; Osteogenesis imperfecta, type XI, OMIM:610968; Osteogenesis imperfecta type 11, MONDO:0012592; Bruck syndrome 1, OMIM:259450 |
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| Fetal anomalies v0.0 | FAM46A |
Zornitza Stark gene: FAM46A was added gene: FAM46A was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: FAM46A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FAM46A were set to Osteogenesis imperfecta, type 18, MONDO:0044329; Osteogenesis imperfecta, type XVIII, OMIM:617952 |
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| Fetal anomalies v0.0 | CREB3L1 |
Zornitza Stark gene: CREB3L1 was added gene: CREB3L1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CREB3L1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CREB3L1 were set to Osteogenesis imperfecta, type XVI, 616229 |
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| Fetal anomalies v0.0 | WNT1 |
Zornitza Stark gene: WNT1 was added gene: WNT1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: WNT1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WNT1 were set to Osteogenesis imperfecta, type XV, OMIM:615220 |
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| Fetal anomalies v0.0 | SLC10A7 |
Zornitza Stark gene: SLC10A7 was added gene: SLC10A7 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SLC10A7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC10A7 were set to 29878199; 30082715 Phenotypes for gene: SLC10A7 were set to Chondrodysplasia with multiple dislocations and amelogenesis imperfecta |
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| Fetal anomalies v0.0 | PPIB |
Zornitza Stark gene: PPIB was added gene: PPIB was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PPIB was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PPIB were set to Osteogenesis imperfecta, type IX 259440 |
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| Fetal anomalies v0.0 | P3H1 |
Zornitza Stark gene: P3H1 was added gene: P3H1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: P3H1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: P3H1 were set to OSTEOGENESIS IMPERFECTA, TYPE VIII |
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| Fetal anomalies v0.0 | LTBP3 |
Zornitza Stark gene: LTBP3 was added gene: LTBP3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: LTBP3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LTBP3 were set to PLATYSPONDYLY WITH AMELOGENESIS IMPERFECTA |
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| Fetal anomalies v0.0 | IFITM5 |
Zornitza Stark gene: IFITM5 was added gene: IFITM5 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: IFITM5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: IFITM5 were set to OSTEOGENESIS IMPERFECTA TYPE V |
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| Fetal anomalies v0.0 | GNAS |
Zornitza Stark gene: GNAS was added gene: GNAS was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: GNAS were set to ALBRIGHT HEREDITARY OSTEODYSTROPHY; GNAS HYPERFUNCTION; PSEUDOHYPOPARATHYROIDISM TYPE 1B; ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA |
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| Fetal anomalies v0.0 | FTL |
Zornitza Stark gene: FTL was added gene: FTL was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: FTL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: FTL were set to HEREDITARY HYPERFERRITINEMIA-CATARACT SYNDROME |
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| Fetal anomalies v0.0 | FAM20A |
Zornitza Stark gene: FAM20A was added gene: FAM20A was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: FAM20A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FAM20A were set to AMELOGENESIS IMPERFECTA AND GINGIVAL FIBROMATOSIS SYNDROME |
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| Fetal anomalies v0.0 | ERF |
Zornitza Stark gene: ERF was added gene: ERF was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ERF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ERF were set to Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia; COMPLEX CRANIOSYNOSTOSIS |
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| Fetal anomalies v0.0 | CRTAP |
Zornitza Stark gene: CRTAP was added gene: CRTAP was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CRTAP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CRTAP were set to Osteogenesis imperfecta, type VII 610682 |
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| Fetal anomalies v0.0 | COL1A2 |
Zornitza Stark gene: COL1A2 was added gene: COL1A2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: COL1A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: COL1A2 were set to Osteogenesis imperfecta; Ehlers-Danlos syndrome |
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| Fetal anomalies v0.0 | COL1A1 |
Zornitza Stark gene: COL1A1 was added gene: COL1A1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: COL1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: COL1A1 were set to OSTEOGENESIS IMPERFECTA TYPE III; CAFFEY DISEASE; OSTEOGENESIS IMPERFECTA TYPE I; OSTEOGENESIS IMPERFECTA TYPE IIA; EHLERS-DANLOS SYNDROME TYPE VIIA; COL1A1/2-RELATED OSTEOGENESIS IMPERFECTA; EHLERS-DANLOS SYNDROME, CLASSIC TYPE, COL1A1-RELATED |
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| Fetal anomalies v0.0 | BMP1 |
Zornitza Stark gene: BMP1 was added gene: BMP1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: BMP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BMP1 were set to 28513615 Phenotypes for gene: BMP1 were set to Osteogenesis imperfecta type XIII 614856 |
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| Fetal anomalies v0.0 | ADAR |
Zornitza Stark gene: ADAR was added gene: ADAR was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ADAR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: ADAR were set to AICARDI-GOUTIERES SYNDROME ASSOCIATED WITH A TYPE I INTERFERON SIGNATURE; DYSCHROMATOSIS SYMMETRICA HEREDITARIA 1 |
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