Novel SCN9A variant associated with congenital insensitivity to pain

Mol Biol Rep. 2023 Jul;50(7):6293-6298. doi: 10.1007/s11033-023-08507-0. Epub 2023 May 25.

Abstract

Background: Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characterized by lack of pain perception and a wide spectrum of clinical signs such as anosmia and hyposmia. Variants in SCN9A gene are associated with CIP. We here report on a Lebanese family with three CIP patients referred for genetic investigations.

Methods and results: Whole exome sequencing analysis revealed the presence of a novel nonsense, homozygous SCN9A pathogenic variant: SCN9A (NM_001365536.1): c.4633G > T, p.(Glu1545*) in exon 26.

Conclusion: Our three Lebanese patients had CIP, urinary incontinence and normal olfactory function while two of them also presented with osteoporosis and osteoarthritis; this association of features has not been previously reported in the literature. We hope that this report would contribute to a better delineation of the phenotypic spectrum associated with SCN9A pathogenic variants.

Keywords: Congenital insensitivity to Pain; Lebanese; SCN9A gene; Urinary incontinence; Whole exome sequencing.

MeSH terms

  • Channelopathies*
  • Exons
  • Humans
  • Mutation
  • NAV1.7 Voltage-Gated Sodium Channel / genetics
  • Pain / genetics
  • Pain Insensitivity, Congenital* / genetics

Substances

  • SCN9A protein, human
  • NAV1.7 Voltage-Gated Sodium Channel

Supplementary concepts

  • Indifference to Pain, Congenital, Autosomal Recessive