Genome sequencing identifies biallelic variants in SCLT1 in a patient with syndromic nephronophthisis: Reflections on the SCLT1‐related ciliopathy spectrum

• Published in: American journal of medical genetics. Part A 2024-11, Vol.194 (11), p.e63789-n/a
• Main Authors: Gillesse, E., Wade, A., Parboosingh, J. S., Au, P. Y. B., Bernier, F. P., Lamont, R. E., Innes, A. M.
• Format: Article
• Language: English
• Subjects: Alleles; Bardet-Biedl Syndrome - diagnosis; Bardet-Biedl Syndrome - genetics; Bardet-Biedl Syndrome - pathology; Bardet–Biedl; Child; Ciliopathies - genetics; Ciliopathies - pathology; ciliopathy; Clathrin; Female; genome sequencing; Humans; Kidney Diseases, Cystic - genetics; Kidney Diseases, Cystic - pathology; Leber Congenital Amaurosis; Male; Mutation - genetics; Nephronophthisis; Optic Atrophies, Hereditary; Phenotype; Senior–Loken; syndrome delineation; Whole Genome Sequencing
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.63789

Ciliopathies represent a major category of rare multisystem disease. Arriving at a specific diagnosis for a given patient is challenged by the significant genetic and clinical heterogeneity of these conditions. We report the outcome of the diagnostic odyssey of a child with obesity, renal, and retinal disease. Genome sequencing identified biallelic splice site variants in sodium channel and clathrin linker 1 (SCLT1), an emerging ciliopathy gene. We review the literature on all patients reported with biallelic SCLT1 variants highlighting a frequent clinical presentation that overlaps Bardet–Biedl and Senior–Loken syndromes. We also discuss current concepts in syndrome designation in light of these data.