Identification of novel variations in the NTRK1 gene causing congenital insensitivity to pain with anhidrosis

Background Congenital insensitivity to pain (CIP) conditions are a group of Mendelian disorders with clinical and genetic heterogeneity. CIP with anhidrosis (CIPA) is a distinct subtype caused by biallelic variants in the NTRK1 gene. Methods In this study, six families with CIPA were recruited and submitted to a series of clinical and genetic examinations. Whole‐exome sequencing and whole‐genome sequencing were applied to perform a comprehensive genetic analysis. Sanger sequencing was used as a validation method. Results These patients exhibited phenotypic variability. All probands in the six families were positive for biallelic pathogenic variants in NTRK1 . Five individual variants, namely NTRK1 : (NM_002529.3) c.851‐33T>A, c.717+2T>C, c.1806‐2A>G, c.1251+1G>A, and c.851‐794C>G, including three novel ones, were identified, which were carried by the six patients in a homozygous or compound heterozygous way. The validation results indicated that all the parents of the six probands, except for one father and one mother, were monoallelic carriers of a single variant. Conclusions The findings in our study extended the variation spectrum of the NTRK1  gene and highlighted the advantage of the integrated application of multiplatform genetic technologies.