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Paramyotonia congenita: From clinical diagnosis to in silico protein modeling analysis
Author(s) -
Nurputra Dian K.,
Nakagawa Taku,
Takeshima Yasuhiro,
Harahap Indra S.K.,
Morikawa Satoru,
Sakaeda Toshiyuki,
Lai Poh San,
Matsuo Masafumi,
Takaoka Yutaka,
Nishio Hisahide
Publication year - 2012
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/j.1442-200x.2012.03646.x
Subject(s) - missense mutation , in silico , medicine , myotonia congenita , mutation , protein structure prediction , myotonia , genetics , mutation testing , bioinformatics , computational biology , protein structure , biology , biochemistry , gene , myotonic dystrophy
Background: Paramyotonia congenita (PMC) is an autosomal dominant disorder characterized by cold‐ or exercise‐induced myotonia. PMC is caused by a mutation in SCN4A which encodes the α‐subunit of the skeletal muscle sodium channel. Methods: The patient was an 11‐year‐old Japanese girl who was diagnosed as having PMC. To confirm the diagnosis, an orbital ice‐pack test and blinking tests were performed. Next, to identify the mutation, genetic analysis of SCN4A was performed. Finally, to evaluate the mutation effect on the protein structure, in silico protein modeling analysis was performed. Results: Cold‐ and exercise‐induced myotonia was reproduced in the patient with non‐invasive bedside tests: ice‐pack and blinking tests. In the genetic analysis, a missense mutation, c.4343G>A in SCN4A , was identified, which may result in an arginine to histidine substitution at 1448 in the protein sequence (p.Arg1448His). According to the protein modeling analysis, the mutation neutralized the positive electrostatic charge at 1448 in the DIV/S4 segment and disrupted the beginning of the helical structure in the DIV/S3‐S4 linker of the SCN4A protein. Conclusions: Diagnostic physical interventions in the patient confirmed the phenotype presentation consistent with PMC, and the in silico protein modeling analysis of p.Arg1448His predicted structural changes which can affect function of the protein. All the data confirmed the diagnosis of PMC in the patient and added to existing literature emphasizing the important role of arginine residue at 1448.