Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): Genetic and clinical characterization

FLORENCIA GILIBERTO ; PAMELA RADIC; LEONELA N LUCE; VERÓNICA FERREIRO; DE BRASSI CARLOS; , SZIJAN IRENE

JOURNAL OF THE NEUROLOGICAL SCIENCES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2013

0022-510X

Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by early muscular degeneration and death. DMD usually affects males, being the females asymptomatic carriers of mutations. However, some of them manifest symptoms as a result of translocation between X chromosome and an autosome or of heterozygous mutations that cause a randomly inactivation of most of their normal X chromosome Methods: Six symptomatic female carriers were analyzed by segregation of STRs-(CA)n, MLPA and X chromosome inactivation pattern assays. Results: The females shared mild muscular weakness, high SCK and low muscle dystrophin levels. Segregation of STRs-(CA)n showed a hemizygous pattern in three patients, confirmed by MLPA, which also show a duplication in another patient. X-chromosome inactivation analysis showed an extremely skewed X inactivation pattern in the six females. Discussion: Our results suggest that the DMD phenotype in female carriers of a dystrophin mutation correlates with a skewed X-chromosome inactivation pattern.