Novel SCN9A variant associated with congenital insensitivity to pain

Abstract

BackgroundCongenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characterized by lack of pain perception with a wide spectrum of clinical signs such as anosmia and hyposmia. SCN9A gene variants were found to be associated with CIP. We here report on a family with three CIP affected patients referred for genetic investigations. Methods and ResultsWhole 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. ConclusionOur 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 spectrum caused by SCN9A pathogenic variants.

Pathology of pain and its implications for therapeutic interventions

“…Mutations of multiple sites of Scn9a gene cause truncation or function loss of Nav1.7, leading to congenital insensitivity to pain. Some cases are complicated with anosmia, while other patients have normal olfactory sensation, 159 – 161 suggesting that mechanisms by which Nav1.7 modulates pain and olfaction partially overlap. Common missense mutants of Scn9a are correlated with pain severity of clinical patients with symptomatic disc herniation.…”