• F Zhao, B Mao, X Geng, X Ren, Y Wang, Y Guan, S Li, L Li, S Zhang, Y You, Y Cao, T Yang, and X Zhao.
• Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
• Eur. J. Neurol. 2020 Aug 1; 27 (8): 1697-1705.

Background And PurposeHereditary sensory and autonomic neuropathies (HSANs) are a group of clinically and genetically heterogeneous neurological disorders characterized by sensory dysfunctions. Here, 21 affected Chinese families are reported, including 19 with congenital insensitivity to pain with anhidrosis (CIPA; namely HSAN IV) and two with congenital insensitivity to pain (CIP; namely HSAN IID) caused by biallelic variations in NTRK1 and SCN9A, respectively, aiming to identify causative variants in these families and compare how different variants in NTRK1 affect the function of tropomyosin receptor kinase A (TrkA).MethodsRecombinant plasmids harboring the wild-type and six mutant alleles (p.Gln216*, p.Glu584Lys, p.Leu595Arg, p.Pro684Leu, p.Val709Leu and p.Arg765Cys) of NTRK1 cDNA were constructed and transfected into HEK293 cells.ResultsThe results suggested that the five missense variants only presented a subtle influence on the expression level and glycosylation of TrkA but compromised the receptor phosphorylation. Our findings also suggested that a synonymous variant c.219C>T in NTRK1 may cause aberrant splicing, indicating a potential novel pathogenic mechanism of CIPA. Furthermore, gross deletion of SCN9A was first associated with CIP.ConclusionsThis study identified multiple forms of variants responsible for CIPA/CIP in the Chinese population and might provide new insights into the pathogenesis of CIPA.© 2020 European Academy of Neurology.

21 keywords...

hide…