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| Fetal anomalies v0.4266 | CENPE |
Ain Roesley gene: CENPE was added gene: CENPE was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CENPE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CENPE were set to 24748105; 30086807 Phenotypes for gene: CENPE were set to Microcephaly 13, primary, autosomal recessive (MIM#616051) Review for gene: CENPE was set to RED gene: CENPE was marked as current diagnostic Added comment: PMID: 24748105; - 2 siblings from non-consanguineous family of European descent - patient A: at birth, OFC of -5SD which progressed to -9SD at 5 years of age - patient B: no measurement at birth but OFC was -7SD at 3 years of age - cHet for 2 missense *no new reports since. A review of AR primary microcephaly in 2018 still states just 1 family (PMID: 30086807) Sources: Literature |
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| Fetal anomalies v0.3908 | PLOD3 |
Krithika Murali gene: PLOD3 was added gene: PLOD3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PLOD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLOD3 were set to 30237576; 18834968 Phenotypes for gene: PLOD3 were set to Lysyl hydroxylase 3 deficiency - MIM#612394 Review for gene: PLOD3 was set to GREEN Added comment: 4 unrelated families reported with biallelic PLOD3 variants and Stickler-syndrome like phenotype including antenatal phenotype of IUGR in one family. -- PMID 30237576 Maddirevula et al 2019 - report homozygous nonsense variant in a proband with dysmorphic facies, microcephaly, ptosis and contractures. No antenatal information provided. PMID 31129566 Ewans et al 2019 - report 3 affected siblings with a Stickler-syndrome like disorder. - Patient 1 had congenital nystagmus and presented with hearing loss and myopia. On examination aged 2, noted to have dysmorphic features - prominent eyes, hypertelorism, malar hypoplasia, an upturned nose, low-set ears and microretrognathia. - Patient 2 noted to have camptodactyly and clinodactyly postnatally. On examination age 5 noted to have DIP joint contractures and mild skin syndactyly. - Patient 3 - breech delivery. bilateral hand foot camptodactyly, facial dysmorphism. - No antenatal features reported. PMID 30463024 Vahidnehzad et al 2019 - report a male proband from a consanguineous Iranian Baloch family referred for assessment age 4.5. Noted to have developmental delay, musculoskeletal manifestations including scoliosis, flexion contractions, cutaneous syndactyly, right diaphragmatic eventration, ocular anomalies, growth failure and skin blisters. No concerns antenatally. Postnatally noted to have cataract and facial dysmorphism (midface hypoplasia). Homozygous PLOD3 missense variant identified, parents unaffected carriers. PLOD3 mRNA levels in the patient’s fibroblasts measured by whole-transcriptome sequencing and confirmed by RT-PCR, were the same as in control cells, however, the expression of type VII collagen was reduced significantly. No antenatal features reported. PMID: 18834968 Salo et al 2008 - a female proband with significant IUGR, characteristic craniofacial profile, diaphragm eventration, skeletal anomalies (bilateral talipes equinovarus, flexion contractures, scoliosis from age 7), skin anomalies incl blistering and ocular anomalies. One 28 week male stillborn sibling noted to have significant IUGR and skeletal anomalies on post-mortem. Supportive functional evidence. Compound het PLOD3 variants. Sources: Literature |
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| Fetal anomalies v0.3693 | HDAC4 |
Zornitza Stark changed review comment from: Contradictory evidence: deletions linked to brachydactyly-MR but note some individuals reported without MR. Only two reports of intragenic variants (still structural rather than SNVs).; to: Contradictory evidence: deletions linked to brachydactyly-MR but note some individuals reported without MR. Only two reports of intragenic variants (still structural rather than SNVs). Subtle brain abnormalities, hip dislocation reported in PMID 33537682. |
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| Fetal anomalies v0.2951 | G6PD |
Krithika Murali gene: G6PD was added gene: G6PD was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: G6PD 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: G6PD were set to 1316704; 26279483; 18177777; 17825683; 1127504; 7472841 Phenotypes for gene: G6PD were set to Haemolytic anaemia, G6PD deficient (300908) Review for gene: G6PD was set to AMBER Added comment: Well-known association with G6PD deficiency. Borderline red-amber gene for fetal anomalies. However, as features of anaemia can sometimes be detected in fetus antenatally and therapeutic/maternal trigger avoidance options available, I have favoured amber rating. PMID: 26279483 Keller et al 2015 - report a mother who is a carrier for a G6PD variant (Guadalajara variant) with a family history of a brother and paternal uncle who died as neonates from severe hydrops. She was counselled to avoid substances that could precipitate oxidative stress from 22 weeks gestation onwards. During her first pregnancy, a male fetus was found to have mild cardiomegaly at 31 weeks with elevated MCAPSV - suggestive of anaemia. Intrauterine transfusion instituted. Presence of maternally inherited G6PD variant confirmed in the fetus. There are other case reports of hydrops fetalis presumed secondary to G6PD deficiency but evidence is limited.. 4999390; 1127504 - older studies, no genomic confirmation available. 4999390 Perkins et al 1971 - Mother presumed to be a carrier for G6PD deficiency and all 3 babies presumed to have the same - 1st child neonatal jaundice with abnormal G6PD test result and death at 59 days of life from undetermined cause - 2nd pregnancy - mother given sulfizoxazole for UTI during pregnancy, delivered stillborn infant at 36 weeks with hydrops fetalis and severe anaemia - 3rd child - well, neonatal jaundice and abnormal G6PD test. Mother O neg blood group, all three babies +ve blood group, DAT -ve and RhoGam given each pregnancy. 1127504 - Mentzer and Collier et al 1975 Male infant died at 2 hours of life with evidence of haemolysis and autopsy findings of hydrops. G6PD screening test in baby abnormal. Mother had low-normal G6PD activity, abnormal ascorbate cyanide test, abnormal MTT cytochemical however no abnormal migrating band of G6PD activity was present on electrophoresis. URTI episode during pregnancy, ascorbic acid consumption and fava bean consumption noted. G6PD deficiency presumed in mother and infant but not genomically confirmed. 23719252; 24999569 - Two case reports identified. However, a second diagnosis was present in both and the G6PD deficiency may have contributed to severity rather than being the primary factor. Sources: Literature |
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| Fetal anomalies v0.2539 | TRPM7 |
Zornitza Stark changed review comment from: 4 variants identified in a stillbirth cohort. Some supportive evidence that these variants alter channel function.; to: 4 variants identified in a stillbirth cohort. Ion channel expressed in the nervous and cardiac systems. The variant associated with ALS/dementia in the Guam population, p.Thr1482Ile is present in >23,000 hets in gnomad, which is out of keeping for a rare Mendelian disorder. Note recent publication associating missense variants with cardiac arrhythmia and stillbirth, with some functional data provided to substantiate effect of variant on protein function but not necessarily establish gene-disease association. |
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| Fetal anomalies v0.2539 | TRPM7 | Zornitza Stark reviewed gene: TRPM7: Rating: RED; Mode of pathogenicity: None; Publications: 31423533; Phenotypes: Arrhythmia, stillbirth; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2496 | STIL | Zornitza Stark Marked gene: STIL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2496 | STIL | Zornitza Stark Gene: stil has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2496 | STIL | Zornitza Stark Publications for gene: STIL were set to 29230157 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2495 | STIL | Zornitza Stark Classified gene: STIL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2495 | STIL | Zornitza Stark Gene: stil has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2494 | STIL | Zornitza Stark changed review comment from: More than 10 unrelated families reported.; to: More than 10 unrelated families reported. Brain abnormalities in one. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.612 | ZBTB42 |
Krithika Murali gene: ZBTB42 was added gene: ZBTB42 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: ZBTB42 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZBTB42 were set to 25055871 Phenotypes for gene: ZBTB42 were set to ?Lethal congenital contracture syndrome 6- #616248 Review for gene: ZBTB42 was set to AMBER Added comment: Homozygous missense variant reported in a family with three stillbirths and a phenotype consistent with LCCS. Supportive zebrafish model. Sources: Expert list, Literature |
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| Fetal anomalies v0.0 | TRPM7 |
Zornitza Stark gene: TRPM7 was added gene: TRPM7 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPM7 were set to 32503408; 31423533 Phenotypes for gene: TRPM7 were set to Cardiac arrhythmia, stillbirth |
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| Fetal anomalies v0.0 | STIL |
Zornitza Stark gene: STIL was added gene: STIL was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: STIL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STIL were set to 29230157 Phenotypes for gene: STIL were set to Microcephaly 7, primary, autosomal recessive, MONDO:0012989; Microcephaly 7, primary, autosomal recessive, OMIM:612703 |
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