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An Overview and Update of ATP7A Mutations Leading to Menkes Disease and Occipital Horn Syndrome
Author(s) -
Tümer Zeynep
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22266
Subject(s) - atp7a , menkes disease , biology , genetics , mutation , neurodegeneration , gene , disease , pathology , copper metabolism , medicine , copper , transporter , chemistry , organic chemistry
Menkes disease ( MD ) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar “kinky” hair, are the main manifestations. MD is inherited as an X ‐linked recessive trait, and as expected the vast majority of patients are males. MD occurs because of mutations in the ATP7A gene and the vast majority of ATP7A mutations are intragenic mutations or partial gene deletions. ATP 7 A is an energy‐dependent transmembrane protein, which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper–histidine treatment may correct some of the neurological symptoms. This study reviews 274 published and 18 novel disease causing mutations identified in 370 unrelated MD patients, nonpathogenic variants of ATP7A , functional studies of the ATP7A mutations, and animal models of MD .