2 research outputs found
Female Fabry disease patients and X-chromosome inactivation
Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-
galactosidase A (GLA). Once it was thought to affect only hemizygous males. Over the last fifteen years, research
has shown that most females carrying mutated allele also develop symptoms, demonstrating a wide range of
disease severity, from a virtually asymptomatic to more classical profile, with cardiac, renal, and cerebrovascular
manifestations. This variable expression in females is thought to be influenced by the process of X-chromosome
inactivation (XCI). The aim of this study was to assess severity of the clinical phenotype, to analyze XCI patterns,
and to estimate their effect on disease manifestation in twelve female Fabry disease patients from five unrelated
Polish families. Our analyses revealed that patients presented with the broad range of disease expression - from
mild to severe, and their clinical involvement did not correlate with XCI profiles. Female carriers of the mutation
in the GLA gene with the random XCI may present with the wide range of disease signs and symptoms. Thus, XCI
is not a main factor in the phenotype variability of Fabry disease manifestation in heterozygous females