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| Fetal anomalies v1.195 | SCLT1 |
Rhiannon Mellis gene: SCLT1 was added gene: SCLT1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SCLT1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SCLT1 were set to No OMIM phenotype; Oro-facio-digital syndrome type IX; Senior-Løken Syndrome Review for gene: SCLT1 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Green on related panel(s): Rare multisystem ciliopathy Super panel Copied from rare multisystem ciliopathies panel: PMID: 24285566 - Adly et al 2014 - 1 case with index patient with consanguineous Saudi parents and a severe ciliopathy phenotype. He had severe midline cleft lip and palate, microcephaly and choanal atresia. He also had significant eye involvement in the form of severe coloboma, and congenital heart disease (ASD and VSD). He had micropenis. Brain imaging revealed pachygyria and absent corpus callosum. He had abnormal inner ear structures. A splicing mutation was identified in SCLT1 (, NM_144643.2:exon5:c.290+2T>C). This mutation completely abolishes the consensus donor site of exon 5 as confirmed by RTPCR, which showed complete skipping of exon 5 resulting in a frameshift and introduction of a premature stop codon (p.Lys79Valfs*4), PMID: 28005958 - de Castro-Miró et al 2016 - A cohort of 33 pedigrees affected with a variety of retinal disorders was analysed by WES. 1 case with compound heterozygosity (one missense and one splicing altering mutations) in SCLT1 that segregates with the condition in the family (2 affected siblings). Proposed to be causative of early-onset Retinitis Pigmentosa. SCLT1 is a member of the centrosomal/ciliary protein family. PMID: 28486600 - Li et al 2017 - report a mouse model with mutated Sclt1 gene. The Sclt1-/- mice exhibit typical ciliopathy phenotypes, including cystic kidney, cleft palate and polydactyly. PMID: 30425282 - Katagiri et al 2018 - a patient with Senior Løken syndrome and her unaffected parents revealed that the patient had infantile-onset retinal dystrophy and juvenile-onset nephronophthisis. Other systemic abnormalities included hepatic dysfunction, megacystis, mild learning disability, autism, obesity, and hyperinsulinemia. Whole-exome sequencing identified compound heterozygous SCLT1 variants (c.1218 + 3insT and c.1631A > G) in the patient. The unaffected parents were heterozygous for each variant. Transcript analysis using reverse transcription PCR demonstrated that the c.1218 + 3insT variant leads to exon 14 skipping (p.V383_M406del), while the other variant (c.1631A > G) primarily leads to exon 17 skipping (p.D480EfsX11) as well as minor amounts of two transcripts. Immunohistochemical analysis demonstrated that the Sclt1 protein was localized to the distal appendage of the photoreceptor basal body, indicating a ciliary protein. = 3 cases plus a mouse model and functional evidence that the protein is a ciliary protein. Sources: Literature |
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| Fetal anomalies v0.166 | PTS | Rebecca Foulger edited their review of gene: PTS: Added comment: This gene and phenotype were discussed during review of borderline cases in April 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: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | PTS | Rebecca Foulger reviewed gene: PTS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | PTS |
Rebecca Foulger gene: PTS was added gene: PTS was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PTS were set to 6-PYRUVOYLTETRAHYDROPTERIN SYNTHASE DEFICIENCY |
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