Congenital myasthenic syndrome in Japan: ethnically unique mutations in muscle nicotinic acetylcholine receptor subunits.

Autor: Azuma Y; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan., Nakata T; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan., Tanaka M; Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Shen XM; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Ito M; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan., Iwata S; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan., Okuno T; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan., Nomura Y; Segawa Neurological Clinic for Children, Tokyo, Japan., Ando N; Department of Pediatrics, Nagoya City University Graduate School of Medicine, Nagoya, Japan., Ishigaki K; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan., Ohkawara B; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan., Masuda A; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan., Natsume J; Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan., Kojima S; Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan., Sokabe M; Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Ohno K; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: ohnok@med.nagoya-u.ac.jp.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2015 Jan; Vol. 25 (1), pp. 60-9. Date of Electronic Publication: 2014 Sep 10.
DOI: 10.1016/j.nmd.2014.09.002
Abstrakt: Congenital myasthenic syndromes (CMS) are caused by mutations in genes expressed at the neuromuscular junction. Most CMS patients have been reported in Western and Middle Eastern countries, and only four patients with COLQ mutations have been reported in Japan. We here report six mutations in acetylcholine receptor (AChR) subunit genes in five Japanese patients. Five mutations are novel, and one mutation is shared with a European American patient but with a different haplotype. Among the observed mutations, p.Thr284Pro (p.Thr264Pro according to the legacy annotation) in the epsilon subunit causes a slow-channel CMS. Five other mutations in the delta and epsilon subunits are splice site, frameshift, null, or missense mutations causing endplate AChR deficiency. We also found a heteroallelic p.Met465Thr in the beta subunit in another patient. p.Met465Thr, however, was likely to be polymorphism, because single channel recordings showed mild shortening of channel openings without affecting cell surface expression of AChR, and the minor allelic frequency of p.Met465Thr was 5.1% in the Japanese population. Lack of shared mutant alleles between the Japanese and the other patients suggests that most mutations described here are ethnically unique or de novo in each family.
(Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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