Heterogeneity of clinical features and mutation analysis of NTRK1 in Han Chinese patients with congenital insensitivity to pain with anhidrosis

PURPOSE: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited disorder whose core clinical features consist of no response to noxious stimuli and inability to sweat under any conditions. Our goal was to characterize the details of phenotypic and genotypic features in Chinese CIPA patients. PATIENTS AND METHODS: Personal data and clinical information were investigated by interview and physical examination. DNA was extracted from blood samples of patients and their available familial members and subjected to genetic analysis. RESULTS: A total of 41 Han Chinese CIPA patients from 35 unrelated families were recruited. The distribution of patients was mainly in the central and southern regions of China, with a male to female ratio of 3:1 and a mortality rate of 7.3%. Heterogeneity of clinical features, including pain insensitivity, temperature sensation, and complications, were cataloged. Interestingly, some patients had “visceral pain” sensation, and there was a significant difference in temperature perception and thermal pain between individuals. The incidence of bone and joint fractures was 49%. The characteristics of 19 mutations of NTRK1 in 41 patients, with five novel mutations, were identified. More than 63% of patients had the splice mutation, c.851–33 T>A, which strongly suggests that it may be a common pathogenic site in Han Chinese patients. CONCLUSION: Current findings expand our knowledge about the spectrum of phenotypic features and the racial characteristics of NTRK1 mutations of CIPA patients in the Han Chinese population.