Abstract
SH3TC2, known as the causative gene of autosomal recessive demyelinating Charcot-Marie-Tooth type 4C (CMT4C), was also found linked to a mild mononeuropathy of the median nerve with an autosomal dominant inheritance pattern. Using DNA microarray, Illumina MiSeq, and Ion proton, we carried out gene panel sequencing among 1483 Japanese CMT patients, containing 397 patients with demyelinating CMT. From seven patients with demyelinating CMT, we identified eight recessive variants in the SH3TC2 gene, consisting of five novel (pathogenic/likely pathogenic) and three reported variants. Additionally, from two patients with axonal CMT, we detected a reported recessive variant, p.Arg77Trp, which was herein reclassified as variant with unknown significance. Of the seven CMT4C patients (six females and one male), 2/7 patients developed symptoms at their first decade, and 5/7 patients lost their ambulation around age 50. Scoliosis was observed from more than half (4/7) of these patients, whereas hearing loss is the most common symptom of central nervous system (6/7). No median nerve mononeuropathy was recorded from their family members. We identified recessive variants in SH3TC2 from 1.76% of demyelinating CMT patients. An uncommon gender difference was recognized and the wild spectrum of these variants suggests mutational diversity of SH3TC2 in Japan.
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Acknowledgements
The authors thank the patients and their families for participating in this study and their physicians for submitting the clinical samples. Also the authors thank Mrs. Aya Ebina and Tomoko Onishi for their excellent technical assistant. This study was supported in part by grants from the research on the Nervous and Mental Disorders and Research Committee for Charcot–Marie–Tooth Disease, Neuropathy, Ataxic Disease and Applying Health and Technology of Ministry of Health, Welfare and Labour, Japan. This research is also supported by the Research program for conquering intractable disease from Japan Agency for Medical Research and development (AMED), and JSPS KAKENHI (Grant Number 26461275).
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Yuan, JH., Hashiguchi, A., Okamoto, Y. et al. Clinical and mutational spectrum of Japanese patients with recessive variants in SH3TC2 . J Hum Genet 63, 281–287 (2018). https://doi.org/10.1038/s10038-017-0388-5
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DOI: https://doi.org/10.1038/s10038-017-0388-5
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