Mercier et al. (2013) reviewed the features of 26 female carriers of pathogenic mutations in the DMD gene who were referred for symptoms related to the disorder before 17 years of age. Five had a Duchenne-like phenotype with loss of ambulation before age 15 years, 13 had a Becker-like phenotype with muscle weakness but persistence of ambulation after age 15 years, and 8 had exercise intolerance. Initial symptoms included significant muscle weakness (88%), mostly affecting the lower limbs, or exercise intolerance (27%). Cardiac dysfunction was present in 19%, and cognitive impairment in 27%. Cognitive impairment was associated with mutations in the distal part of the gene. Muscle biopsy showed dystrophic changes in 83% and mosaic immunostaining for dystrophin in 81%. The X-chromosome inactivation pattern was biased in 62% of cases. Mercier et al. (2013) concluded that carrier females may have significant symptoms of the disorder.
Using transient transfection assays, Fan et al. (1999) demonstrated that BRCA1 inhibits signaling by the ligand-activated estrogen receptor ESR-alpha through the estrogen-responsive enhancer element and blocks the C-terminal transcriptional activation function AF2 of ESR-alpha. These results suggested that wildtype BRCA1 protein may function, in part, to suppress estrogen-dependent mammary epithelial proliferation by inhibiting ESR-alpha-mediated transcriptional pathways related to cell proliferation, and that loss of this ability may contribute to tumorigenesis.