Congenital Insensitivity to Pain with Anhydrosis in a Malaysian Family: A Genetic Analysis

Abstract

A Malaysian family with congenital insensitivity to pain with anhydrosis was diagnosed based on clinical symptoms of chronic ulcers, joint deformities, malunited fractures, anhydrosis, and learning disabilities. We detected a compound heterozygous mutation in exon 16: V709L from the mother and G718S from the father. Two novel mutations were identified: at amino acid 709, a change of G to C at nucleotide 2209 (approximately 2209G to C) causing a valine to leucine substitution (V709L), and at amino acid 718, a change of G to A at nucleotide 2236 (approximately 2236G to A) causing a glycine to serine substitution (G718S). Polymorphisms identified were at nucleotides approximately 2113G to C and approximately 2176T to C.

Congenital insensitivity to pain and anhydrosis due to a rare mutation and that is complicated by inflammatory bowel disease and amyloidosis: a case report

“…Other clinical findings consistent with CIPA in this patient included insensitivity to pain, learning disabilities, seizures, joint dislocation, skin ulcers, and chronic osteomyelitis 3, 8, 9. We confirmed the diagnosis of CIPA by genetic testing and detected a mutation in the NTRK1 gene; the NTRK1 c.2125G>T (p.Val709Leu) variant has been reported in a Malaysian patient with CIPA 3 and was predicted to be deleterious by in silico analysis using SIFT (http://sift.jcvi.org/), MutationTatster (http://www.mutationtaster.org/), and MutPred (http://mutpred.mutdb.org/) softwares. Additionally, the p.Val709 is completely conserved across different species.…”

“…Here, we report a male patient with CIPA who showed a rare mutation in the NTRK1 gene that was previously reported once 3. The patient's course was intriguing because it was complicated by inflammatory bowel disease and renal amyloidosis.…”

“…The NTRK1 gene encodes for the high‐affinity neurotrophic tyrosine kinase receptor type 1 (NTRK1), an essential part of the pain pathway 3. Thus far, approximately 50 loss‐of‐function NTRK1 variants have been associated with CIPA 5.…”

Developments in autonomic research: a review of the latest literature

“…It is likely that each variant of HSAN is caused by different genetic errors that determine the phenotype. In the December 2007 issue of the Journal of Orthopedic Surgery, Shalimar and colleagues, from the Department of Orthopaedics and Traumatology in the Faculty of Medicine at Universiti Kebangsaan Malaysia, describe a Malaysian family with congenital insensitivity to pain with anhydrosis, members of which suffered from chronic ulcers, joint deformities, malunited fractures, anhydrosis, and learning disabilities [15]. The authors detected a compound heterozygous mutation in exon 16: V709L from the mother and G718S from the father.…”

Clinical and genetic analysis of Korean patients with congenital insensitivity to pain with anhidrosis

“…4 To date, approximately 50 different NTRK1 mutations have been identified in patients with CIPA from various ethnicities, and some founder mutations have been noted in specific ethnic groups (see Inherited Peripheral Neuropathies Mutation Database website: http://www.molgen.ua.ac.be/CMT-Mutations/). 5,16 So far, 19 nonsense, 14 frameshift, 9 splice-site, and 15 missense mutations, and 1 gross deletion have been detected, suggesting that the pathogenic mechanism could be a loss of function. Although there seems to be no genetic heterogeneity in CIPA, 7 more data are needed to determine the genetic and clinical features of this condition.…”