Variants in the ciliopathy gene SCLT1 are associated with non-syndromic retinal degeneration.

Abstract

Inherited retinal degenerations (IRDs) are a group of clinically and genetically heterogeneous blinding disorders. In this retrospective study, we describe five families with non-syndromic IRD in which affected probands carried rare bi-allelic variants in SCLT1 , a gene previously associated with multiple recessive ciliopathies. Seven of the eight variants identified were novel, and four of them affected splicing, including the known missense p.(Lys544Arg), detected heterozygously in three East Asian probands, and the novel, hypomorphic, deep-intronic variant c.290 + 2732A > G, leading to the inclusion of a 45-bp cryptic exon containing a premature termination codon. Analysis of the genomic data also revealed a large in-frame tandem duplication spanning exon 3-10, which was subsequently validated. Although no clear correlation was found between the severity of the SCLT1- associated phenotypes and the identified causal variants, this report expands the current knowledge of SCLT1 -associated disease by enriching its mutational landscape and supports its association with non-syndromic retinal degeneration.