Symptomatic female carriers of Duchenne muscular dystrophy (DMD): Genetic and clinical characterization

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:336

Article

Giliberto, Florencia¹  Radic, Claudia Pamela²  Luce, Leonela¹  Ferreiro, Veronica³  de Brasi, Carlos²  Szijan, Irene¹ 

[1] Univ Buenos Aires, Fac Farm & Bioquim, RA-1113 Buenos Aires, DF, Argentina

[2] CONICET Acad Nacl Med, Inst Med Expt IMEX, Lab Genet Mol Hemofilia, Buenos Aires, DF, Argentina

[3] Lab Genet Mol Diagnost GENOS SA, Buenos Aires, DF, Argentina

关键词: Duchenne muscular dystrophy;    Symptomatic female carriers;    Clinical symptoms;    Haplotypes;    Mutations;    Skewed X inactivation;   

DOI  :  10.1016/j.jns.2013.09.036

来源: Elsevier

【 摘 要 】

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by mutations in the dystrophin gene and is characterized by muscle degeneration and death. DMD affects males; females being asymptomatic carriers of mutations. However, some of them manifest symptoms due to a translocation between X chromosome and an autosome or to a heterozygous mutation leading to inactivation of most of their normal X chromosome. Six symptomatic female carriers and two asymptomatic were analyzed by: I) Segregation of STRs-(CA)n and MLPA assays to detect a hemizygous alteration, and II) X chromosome inactivation pattern to uncover the reason for symptoms in these females. The symptomatic females shared mild but progressive muscular weakness and increased serum creatin kinase (CK) levels. Levels of dystrophin protein were below normal or absent in many fibers. Segregation of STRs-(CA)n revealed hemizygous patterns in three patients, which were confirmed by MLPA. In addition, this analysis showed a duplication in another patient. X chromosome inactivation assay revealed a skewed X inactivation pattern in the symptomatic females and a random inactivation pattern in the asymptomatic ones. Our results support the hypothesis that the DMD phenotype in female carriers of a dystrophin mutation has a direct correlation with a skewed X-chromosome inactivation pattern. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

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