Favorably skewed X-inactivation accounts for neurological sparing in female carriers of Menkes disease.

ABSTRACT: Classical Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in ATP7A, which is located at Xq13.1-q21. ATP7A encodes a copper-transporting P-type ATPase and plays a critical role in development of the central nervous system. With rare exceptions involving sex chromosome aneuploidy or X-autosome translocations, female carriers of ATP7A mutations are asymptomatic except for subtle hair and skin abnormalities, although the mechanism for this neurological sparing has not been reported. We studied a three-generation family in which a severe ATP7A mutation, a 5.5-kb genomic deletion spanning exons 13 and 14, segregated. The deletion junction fragment was amplified from the proband by long-range polymerase chain reaction and sequenced to characterize the breakp

SUBMITTER: Desai V 

PROVIDER: S-EPMC3099248 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature