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

Am J Med Genet A. 2024 Nov;194(11):e63789. doi: 10.1002/ajmg.a.63789. Epub 2024 Jun 25.

Abstract

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.

Keywords: Bardet–Biedl; Senior–Loken; ciliopathy; genome sequencing; nephronophthisis; syndrome delineation.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Bardet-Biedl Syndrome / diagnosis
  • Bardet-Biedl Syndrome / genetics
  • Bardet-Biedl Syndrome / pathology
  • Child
  • Ciliopathies* / genetics
  • Ciliopathies* / pathology
  • Female
  • Humans
  • Kidney Diseases, Cystic / genetics
  • Kidney Diseases, Cystic / pathology
  • Leber Congenital Amaurosis
  • Male
  • Mutation
  • Optic Atrophies, Hereditary
  • Phenotype
  • Whole Genome Sequencing

Supplementary concepts

  • Senior Loken Syndrome