Skeletal ciliopathies

Gene: SCLT1

Comment on list classification: After consultation with the Genomics England clinical team, removing this gene from the skeletal ciliopathies panel as the skeletal phenotype is not strong.

Created: 15 Nov 2019, 12:36 p.m. | Last Modified: 15 Nov 2019, 12:36 p.m.

Panel Version: 0.18

Comment on list classification: 3 cases plus a mouse model and functional evidence that the protein is a ciliary protein.

Created: 19 Jun 2019, 2:02 p.m.

Not associated with any phenotype in OMIM or Gene2Phenotype.

PMID: 15797711 - this paper does not appear to be about SCLT1 or ciliopathies

PMID: 23348840 - Tanos et al 2013 - identified SCLT1 as a component of distal appendages (DAPs) of centrioles that have been proposed to anchor cilia to the plasma membrane. It is one of five DAP components and is essential for ciliogenesis.

PMID: 24285566 - Adly et al 2014 - 1 case with index patient with consanguineous Saudi parents and a severe ciliopathy phenotype consistent with oro-facio-digital syndrome type IX. 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.

Created: 19 Jun 2019, 2 p.m. | Last Modified: 14 Nov 2019, 1:29 p.m.

Panel Version: 0.15

Green List (high evidence)

Please note two additional individuals reported in these two papers, one with a retinal phenotype, and one with a multi-system phenotype. Also, note animal model data supporting a multi-system ciliopathy.

Created: 7 Aug 2018, 4:40 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 28005958, 24285566, 28486600

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

Mutations only identified in one patient with features of a ciliopathy

Created: 25 Jan 2017, 9:32 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliopathy like disorder

Publications

• 15797711