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Fetal anomalies v6.142 FSD1L Ida Ertmanska gene: FSD1L was added
gene: FSD1L was added to Fetal anomalies. Sources: Literature
Q1_26_promote_green tags were added to gene: FSD1L.
Mode of inheritance for gene: FSD1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FSD1L were set to 41720098; 41720099
Phenotypes for gene: FSD1L were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: FSD1L was set to GREEN
Added comment: PMID: 41720098 Serpieri et al., 2026
Report of eleven individuals (including five fetuses) from six unrelated families harbouring biallelic FSD1L variants. Seq method: exome sequencing. Consanguinity was confirmed in 4/6 families, and suspected in the fifth.
Phenotype spectrum: severe intellectual disability (5/5 assessed from 3 families), epilepsy (5 individuals from 3 families), severe hydrocephalus (3 families), vision deficit due to optic nerve hypoplasia/atrophy (3 families), spastic tetraparesis (2 families) corpus callosum hypoplasia/agenesis on MRI (5/5 families assessed),

Variants detected - largely nonsense type:
Family A - homozygous c.409T>G (p.Leu137Val);
Family B - 3 affected fetuses homozygous for c.1411C>T (p.Gln471Ter);
Family C - sibs compound het for c.1228T>G (p.Phe410Val) and c.1251_1252insTAA (p.Thr418Ter);
Family D - affected individuals (1 fetal case) homozygous for c.1366G>C (p.Asp456His) - shown to impact splicing (r.406_442del), resulting in predicted p.Ser136LeufsTer19 change;
Family E - affected child with homozygous c.835C>T (p.Arg279Ter) change;
Family F - fetus homozygous for c.1260G>A (p.Trp420Ter);

Functional evidence: Fsd1l depletion in mouse embryos recapitulated the ventricular dilation observed in affected fetuses.

PMID 41720099 Lin et al., 2026
Report of 6 affected individuals from 4 families with retinitis pigmentosa. One individual underwent a full neurological evaluation, including brain neuroimaging, which revealed no evidence of central nervous system involvement.
FSD1L variants detected:
Family A: 2 sibs compound het for c.1049G>A (p.Arg350Gln) and c.1428del (p.Phe476Leufs∗22)
Family B: individual comp het for c.488G>A (p.Arg163His), c.488G>A & c.745C>T (p.Arg249∗)
Family C: 2 sibs compound het for c.488G>A (p.Arg163His) & c.226_227del (p.Ser77Argfs∗4)
Family D: individual compound het for c.1037_1038delinsT (p.Pro346Leufs∗8) and c.1025+624_1025+649del
Sibs from family A had mild neurological involvement (mild ID, spastic diplegia in one sibling).
Authors note that "specific combination and functional severity of the two alleles likely determines the clinical outcome", with non-LoF variants causing a milder effect (e.g., isolated retinal phenotype).

FSD1L is not yet associated with a phenotype in OMIM or Gene2Phenotype.
Sources: Literature
Fetal anomalies v1.94 TOGARAM1 Arina Puzriakova gene: TOGARAM1 was added
gene: TOGARAM1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TOGARAM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM1 were set to 32747439
Phenotypes for gene: TOGARAM1 were set to Cleft of the lip and palate; Microphthalmia; Cerebral dysgenesis; Hydrocephalus
Added comment: PMID: 32747439 (2020) - Novel gene-disease association. In two sibling fetuses with a malformation disorder characterised by microcephaly, severe cleft lip and palate, microphthalmia, and brain anomalies, WES revealed compound heterozygous variants ([c.1102C>T, p.Arg368Trp] and [c.3619C>T, p.Arg1207*]) in the TOGARAM1 gene.

Functional analysis of the missense variant in a C. elegans model showed impaired lipophilic dye uptake, with shorter and altered cilia in sensory neurons. In vitro analysis revealed faster microtubule polymerisation compared to wild-type, suggesting aberrant tubulin binding.
Sources: Literature
Fetal anomalies v0.135 ARG1 Rebecca Foulger Source Expert Review Red was added to ARG1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.134 ARG1 Rebecca Foulger edited their review of gene: ARG1: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted ARG1 gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.9 ARG1 Rebecca Foulger reviewed gene: ARG1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.1 ARG1 Rebecca Foulger gene: ARG1 was added
gene: ARG1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: ARG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARG1 were set to ARGININEMIA