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Deep sequencing detects very-low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy.
Miyatake, Satoko; Koshimizu, Eriko; Hayashi, Yukiko K; Miya, Kazushi; Shiina, Masaaki; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Miyake, Noriko; Saitsu, Hirotomo; Ogata, Kazuhiro; Nishino, Ichizo; Matsumoto, Naomichi.
Afiliación
  • Miyatake S; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Koshimizu E; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Hayashi YK; Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Neurophysiology, Tokyo Medical University, Tokyo, Japan.
  • Miya K; Department of Pediatrics, Faculty of Medicine, University of Toyama, Toyama, Japan.
  • Shiina M; Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Nakashima M; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Tsurusaki Y; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Miyake N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Saitsu H; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Ogata K; Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Nishino I; Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • Matsumoto N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: naomat@yokohama-cu.ac.jp.
Neuromuscul Disord ; 24(7): 642-7, 2014 Jul.
Article en En | MEDLINE | ID: mdl-24852243
ABSTRACT
When an expected mutation in a particular disease-causing gene is not identified in a suspected carrier, it is usually assumed to be due to germline mosaicism. We report here very-low-grade somatic mosaicism in ACTA1 in an unaffected mother of two siblings affected with a neonatal form of nemaline myopathy. The mosaicism was detected by deep resequencing using a next-generation sequencer. We identified a novel heterozygous mutation in ACTA1, c.448A>G (p.Thr150Ala), in the affected siblings. Three-dimensional structural modeling suggested that this mutation may affect polymerization and/or actin's interactions with other proteins. In this family, we expected autosomal dominant inheritance with either parent demonstrating germline or somatic mosaicism. Sanger sequencing identified no mutation. However, further deep resequencing of this mutation on a next-generation sequencer identified very-low-grade somatic mosaicism in the mother 0.4%, 1.1%, and 8.3% in the saliva, blood leukocytes, and nails, respectively. Our study demonstrates the possibility of very-low-grade somatic mosaicism in suspected carriers, rather than germline mosaicism.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Miopatías Nemalínicas / Mosaicismo / Mutación Tipo de estudio: Prognostic_studies Límite: Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Neuromuscul Disord Asunto de la revista: NEUROLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Miopatías Nemalínicas / Mosaicismo / Mutación Tipo de estudio: Prognostic_studies Límite: Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Neuromuscul Disord Asunto de la revista: NEUROLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Japón