Identification of founder and novel mutations that cause congenital insensitivity to pain (CIP) in Palestinian patients

Abstract

Congenital insensitivity to pain (CIP) is a rare autosomal recessive disorder, which is characterized primarily by an inability to perceive physical pain from birth, resulting in the accumulation of bruising, inflammation and fractures that affect patient's life expectancy. In Palestine, because of high rate of consanguinity, this rare disease seems to have higher frequency than in other communities. However, there were no systematic studies to address the genetic factors that cause CIP in the Palestinian community. In this study, we genotyped members of five Palestinian CIP-affected families using Sanger and Whole exome sequencing approaches. Our results confirmed the presence of the founder mutation c.1931-ins- T in the NTRK1 gene of Palestinian Bedouin CIPA patients. This mutation was found in three out of the five participating families. In addition, in one CIPA family, we found the missense mutation (c.2170 G > A (G724 S) in exon 16 of NTRK1 gene. Finally, a novel nonsense mutation (c.901A > T, K301*) was detected in exon 7 of the SCN9A gene in CIP without anhidrosis family. In conclusion our study revealed three mutations that caused CIP, and CIPA in Palestinian community which would help in improving the diagnostic and genetic counseling process. And help in building a diagnostic and follow up protocol for the affected individuals, since early diagnosis and medical care interference could prevent a lot of unpleasant complication of CIP, and CIPA patients.

Congenital Insensitivity to Pain with Anhidrosis: A Case Report

“…CIPA is an exceedingly rare disorder, with a reported incidence of one in 125 million [5]. The disease shows geographic variability, which may be attributed to founder mutations and consanguineous marriages [6]. The condition exhibits an autosomal recessive inheritance pattern, necessitating the presence of two mutated alleles for phenotypic expression [7].…”