Novel SCN9A missense mutations contribute to congenital insensitivity to pain: Unexpected correlation between electrophysiological characterization and clinical phenotype.
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| Abstract |
Congenital insensitivity to pain (OMIM 243000) is an extremely rare disorder caused by loss-of-function mutations in SCN9A encoding Nav1.7. Although the SCN9A mutations and phenotypes of painlessness and anosmia/hyposmia in patients are previously well documented, the complex relationship between genotype and phenotype of congenital insensitivity to pain remains unclear. Here, we report a congenital insensitivity to pain patient with novel SCN9A mutations. Functional significance of novel SCN9A mutations was assessed in HEK293 cells expressing Nav1.7, the results showed that p.Arg99His significantly decreased current density and reduced total Nav1.7 protein levels, whereas p.Trp917Gly almost abolished Nav1.7 sodium current without affecting its protein expression. These revealed that mutations in Nav1.7 in this congenital insensitivity to pain patient still retained partial channel function, but the patient showed completely painlessness, the unexpected genotypic-phenotypic relationship of SCN9A mutations in our patient may challenge the previous findings "Nav1.7 total loss-of-function leads to painlessness." Additionally, these findings are helpful for understanding the critical amino acid for maintaining function of Nav1.7, thus contributing to the development of Nav1.7-targeted analgesics.
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| Authors | Jiaoli Sun, Lulu Li, Luyao Yang, Guangyou Duan, Tingbin Ma, Ningbo Li, Yi Liu, Jing Yao, Jing Yu Liu, Xianwei Zhang |
| Journal | Molecular pain (Mol Pain) 2020 Jan-Dec Vol. 16 Pg. 1744806920923881 ISSN: 1744-8069 [Electronic] United States |
| PMID | 32420800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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