Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.
Hum Mol Genet
; 6(9): 1499-504, 1997 Sep.
Article
em En
| MEDLINE
| ID: mdl-9285787
ABSTRACT
A candidate gene, myotubularin, involved in the pathogenesis of X-linked myotubular myopathy (MTM1) was isolated recently. Mutations originally were identified in 12% of patients examined for 40% of the coding sequence, raising the possibility that additional genes could be responsible for a proportion of X-linked cases. We report here the identification of mutations in 26 of 41 independent male patients with muscle biopsy-proven MTM, by direct genomic sequencing of 92% of the known coding sequence of the myotubularin gene. Eighteen patients had point mutations, including one A/G transition found in four patients which alters a splice acceptor site in exon 12 and leads to a three amino acid insertion. Six patients had small deletions involving <6 bp, while two larger deletions encompassed two or six exons, respectively. No differences were noted among the types of mutations between familial and sporadic cases. However, all of the five patients with a mild phenotype had missense mutations. While 50% of the mutations were found in exons 4 and 12, and three distinct mutations were found in more than one patient, no single mutation accounted for more than 10% of the cases. The low frequency of large deletions and the varied mutations identified suggest that direct mutation screening for molecular diagnosis may require gene sequencing.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomo X
/
Proteínas Tirosina Fosfatases
/
Mutação Puntual
/
Debilidade Muscular
/
Ligação Genética
/
Hipotonia Muscular
Limite:
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos