Novel splice site and nonsense variants in INVS cause infantile nephronophthisis

Gene. 2020 Mar 1:729:144229. doi: 10.1016/j.gene.2019.144229. Epub 2019 Nov 7.

Abstract

Nephronophthisis is an autosomal recessive disease characterized by cystic kidney disease with progression to end-stage kidney disease in children and adolescents with or without extra-renal involvement. It is caused by biallelic pathogenic variants in 19 genes including INVS that encodes a ciliary protein essential for renal development and left-right axis establishment. We report a child with bilateral enlarged, echogenic, polycystic kidneys with end-stage renal disease, anemia and metabolic acidosis caused by biallelic novel pathogenic variants, c.796 + 5G > A and c.1789C > T in INVS. We show that the variant, c.796 + 5G > A disrupts the canonical splicing and nonsense variant, c.1789C > T results in nonsense mediated decay.

Keywords: Echogenic kidneys; INVS; Nephronophthisis; Nonsense mediated decay.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Codon, Nonsense
  • Female
  • Gene Frequency
  • Genetic Variation
  • Homozygote
  • Humans
  • Kidney Diseases, Cystic / genetics*
  • Kidney Diseases, Cystic / metabolism
  • Mutation
  • RNA Splice Sites
  • RNA Splicing
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Codon, Nonsense
  • INVS protein, human
  • RNA Splice Sites
  • Transcription Factors

Supplementary concepts

  • Nephronophthisis 2