| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fetal anomalies v0.3412 | SPTBN2 | Zornitza Stark Phenotypes for gene: SPTBN2 were changed from Infantile ataxia with oculomotor and pyramidal signs; SCA14; Spinocerebellar ataxia, autosomal recessive 14, 615386 to Spinocerebellar ataxia 5 (MIM#600224); Spinocerebellar ataxia, autosomal recessive 14 (MIM#615386) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3238 | GPAA1 |
Zornitza Stark changed review comment from: At least 5 unrelated families reported with bi-allelic variants in this gene and delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.; to: At least 5 unrelated families reported with bi-allelic variants in this gene and delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. Clinical presentation is typically post-natal. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3006 | PGM3 |
Zornitza Stark changed review comment from: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation. Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity. More than 10 unrelated families reported. Typically presents post-natally.; to: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation. Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity. More than 10 unrelated families reported. Typically presents post-natally. However, more severe presentations with skeletal abnormalities and congenital malformations reported in PMID 28543917 and 24931394. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3003 | PGM3 |
Zornitza Stark changed review comment from: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation. Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity. More than 10 unrelated families reported.; to: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation. Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity. More than 10 unrelated families reported. Typically presents post-natally. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2489 | SUFU |
Zornitza Stark edited their review of gene: SUFU: Added comment: Rib anomalies and cleft palate are a feature of the mono-allelic disorder. The signs of the bi-alellic disorder are relatively subtle and unlikely to be detectable antenatally.; Changed rating: GREEN; Changed phenotypes: Basal cell nevus syndrome, MIM# 109400; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2257 | HYLS1 |
Zornitza Stark changed review comment from: A recurring homozygous missense variant p.Asp211Gly has been identified in at least 64 cases of hydrolethalus syndrome, described as a Finnish founder mutation (PMID: 15843405, PMID: 18648327). Functional studies in human and patient cells have shown mislocalisation of the protein to the nucleus (PMID: 15843405, PMID: 19400947). Functional studies in c. elegans showed that this variant impaired ciliogenesis (PMID: 19656802). Functional studies in drosophila showed that deletion of HYLS1 led to cilia dysfunction (PMID: 32509774). 2 homozygous living siblings (stop-loss, extension variant p.Ter300TyrextTer11) both diagnosed with Joubert syndrome. Patients had molar tooth signs and dysplasia of cerebellar vermis (PMID: 26830932). No other variants have been reported as pathogenic in this gene. Amber rating given only single founder variant reported with a hydrocephalus phenotype with supporting functional data from multiple animal models indicative of ciliopathy.; to: A recurring homozygous missense variant p.Asp211Gly has been identified in at least 64 cases of hydrolethalus syndrome, described as a Finnish founder mutation (PMID: 15843405, PMID: 18648327). Functional studies in human and patient cells have shown mislocalisation of the protein to the nucleus (PMID: 15843405, PMID: 19400947). Functional studies in c. elegans showed that this variant impaired ciliogenesis (PMID: 19656802). Functional studies in drosophila showed that deletion of HYLS1 led to cilia dysfunction (PMID: 32509774). 2 homozygous living siblings (stop-loss, extension variant p.Ter300TyrextTer11) both diagnosed with Joubert syndrome. Patients had molar tooth signs and dysplasia of cerebellar vermis (PMID: 26830932). No other variants have been reported as pathogenic in this gene. Overall, sufficient evidence that variants in this gene cause a ciliopathy. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1623 | APOPT1 |
Zornitza Stark changed review comment from: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time. Clinical presentation is typically in childhood.; to: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time. Clinical presentation is typically in early childhood. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1623 | APOPT1 |
Zornitza Stark changed review comment from: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time.; to: 6 individuals from 5 unrelated families reported, presenting in late infancy or early childhood with evidence of complex IV deficiency. Phenotype varied widely. Five individuals had episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. The sixth individual never developed neurologic signs. Three had normal cognition and 3 had impaired cognition. Brain imaging showed a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilized or even improved over time. Clinical presentation is typically in childhood. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1469 | SPEN |
Krithika Murali gene: SPEN was added gene: SPEN was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPEN were set to 33596411 Phenotypes for gene: SPEN were set to Radio-Tartaglia syndrome - MIM#619312 Review for gene: SPEN was set to GREEN Added comment: Radio et al. (2021) reported heterozygous SPEN variants in 34 individuals from 33 unrelated families with had global developmental delay, ID, behavioural issues and dysmorphic features. Other features included hypotonia, gait imbalance, pyramidal signs and seizures. Findings potentially ascertainable antenatally: - Brain imaging abnormalities include polymicrogyria, heterotopia, cerebellar atrophy, periventricular white matter defects, agenesis of the corpus callosum, and tethered cord. - Congenital heart defects also present in a significant proportion. Sources: Expert list, Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.848 | GNS | Zornitza Stark Marked gene: GNS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.848 | GNS | Zornitza Stark Gene: gns has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.848 | GNS | Zornitza Stark Phenotypes for gene: GNS were changed from MUCOPOLYSACCHARIDOSIS TYPE 3D to Mucopolysaccharidosis type IIID, MIM# 252940; Sanfilippo syndrome type D, MONDO:0009658 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.847 | GNS | Zornitza Stark Publications for gene: GNS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.823 | GNS | Ain Roesley reviewed gene: GNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12573255, 12624138, 31536183, 25851924; Phenotypes: Mucopolysaccharidosis type IIID, MIM# 252940, Sanfilippo syndrome type D, MONDO:0009658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | SPTBN2 |
Zornitza Stark gene: SPTBN2 was added gene: SPTBN2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: SPTBN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPTBN2 were set to 28636205; 29196973 Phenotypes for gene: SPTBN2 were set to Infantile ataxia with oculomotor and pyramidal signs; SCA14; Spinocerebellar ataxia, autosomal recessive 14, 615386 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | MICU1 |
Zornitza Stark gene: MICU1 was added gene: MICU1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: MICU1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MICU1 were set to MYOPATHY WITH EXTRAPYRAMIDAL SIGNS |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | GNS |
Zornitza Stark gene: GNS was added gene: GNS was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: GNS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GNS were set to MUCOPOLYSACCHARIDOSIS TYPE 3D |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||