Compound heterozygous splice site variants in the SCLT1 gene highlight an additional candidate locus for Senior-Loken syndrome.

ABSTRACT: Senior Løken syndrome (SLS) is a heterogeneous disorder characterized by severe retinal degenerations and juvenile-onset nephronophthisis. Genetic variants in ten different genes have been reported as the causes of SLS. Clinical evaluation of a patient with SLS 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 (6?bps deletion in the last of exon 17 [p.V543_K544del] and exons 17 and 18 skipping [p.D480E, S481_K610del]). Immunohistochemical analysis demonstrated that the Sclt1 protein was localized to the distal appendage of the photoreceptor basal body, indicating a ciliary protein. In conclusion, we identified compound heterozygous splice site variants of SCLT1 in a patient with a new form of ciliopathies that exhibits clinical features of SLS.

SUBMITTER: Katagiri S 

PROVIDER: S-EPMC6233217 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature