Deep sequencing detects very-low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy.
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Miopatías Nemalínicas
/
Mosaicismo
/
Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Child
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Child, preschool
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Female
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Humans
/
Male
Idioma:
En
Revista:
Neuromuscul Disord
Asunto de la revista:
NEUROLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón