A new mutation in NTRK1 gene is associated with congenital insensitivity to pain without anhidrosis

Abstract

Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare autosomal recessive disease characterized by pain insensitivity, frequent intermittent fevers, anhidrosis, self-mutilating actions and mental retardation. Germline mutations in NTRK1 gene have been associated with CIPA. In the current study, we describe the first reported case from Iran. The patient was a 10 month old girl born to a healthy consanguineous Iranian parent with family history of CIPA. Unexpectedly, the cases had normal sweating. Whole exome sequencing revealed a new likely pathogenic mutation in the exon 13 of NTRK1 gene (NM_002529.3) in the proband in homozygote state (c.1524_1531dupGGACATCG, p.Val511Glyfs*39). The frameshift mutation leads to early termination of the coding sequence, which is anticipated to affect the protein function. Sanger sequencing confirmed the results in the proband and other affected members of the family. In addition, Sanger sequencing showed that parents carry the same mutation in heterozygote state. The current study shows a different phenotypic variant of CIPA in Iranian population and adds to the repository NTRK1 mutations.