Identification of novel variations in the NTRK1 gene causing congenital insensitivity to pain with anhidrosis
| Autor: | Xu Chen, Zhan-Ke Feng, Huaying Hu, Jun‐Jun Xu, Ya‐zhou Li, Yong-qing Sun, Kai Yang, Dong‐liang Zhang, Shang Li |
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| Rok vydání: | 2021 |
| Předmět: |
congenital insensitivity to pain with anhidrosis
Pain Insensitivity Congenital QH426-470 Biology Compound heterozygosity Genetic analysis symbols.namesake Congenital insensitivity to pain with anhidrosis Genetics medicine Humans NTRK1 gene Hereditary Sensory and Autonomic Neuropathies Receptor trkA Anhidrosis Molecular Biology Genetics (clinical) Exome sequencing Hypohidrosis Sanger sequencing Genetic heterogeneity Original Articles medicine.disease Mutation symbols Original Article whole‐exome sequencing medicine.symptom whole‐genome sequencing Congenital insensitivity to pain |
| Zdroj: | Molecular Genetics & Genomic Medicine, Vol 9, Iss 11, Pp n/a-n/a (2021) Molecular Genetics & Genomic Medicine |
| ISSN: | 2324-9269 |
| DOI: | 10.1002/mgg3.1839 |
| Popis: | 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. In this study, we recruited six families with probands displaying congenital insensitivity to pain with anhidrosis. A comprehensive genetic detection was performed, and the diagnostic variants were identified. |
| Databáze: | OpenAIRE |
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