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ATP 7A mutations in 66 Japanese patients with Menkes disease and carrier detection: A gene analysis
Author(s) -
Fujisawa Chie,
Kodama Hiroko,
Hiroki Tomoko,
Akasaka Yoshikiyo,
Hamanoue Makoto
Publication year - 2019
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.13817
Subject(s) - mutation , gene , menkes disease , medicine , exon , polymerase chain reaction , genetics , microbiology and biotechnology , genetic analysis , biology , copper metabolism , chemistry , copper , organic chemistry
Abstract Background Menkes disease ( MNK ; MIN 309400) is an X‐linked recessive lethal disorder of copper metabolism caused by mutations in ATP 7A ( MIM 300011), which encodes a transmembrane copper‐transporting P‐type ATP ase. This study assessed mutations in ATP 7A in Japanese patients with MNK and their families using gene analysis. Methods A total of 66 patients with MNK born between 1975 and 2013 in Japan were investigated in this study. Definite diagnosis of MNK was carried out on polymerase chain reaction ( PCR ) amplification and direct sequencing of each exon. Genetic analysis was also performed on 39 women for carrier diagnosis, and on nine fetuses and 10 neonates for the diagnosis of MNK . Results We detected 55 different mutations, of which 20 were de novo mutations. The mutations were located around the six copper binding sites, first to third and six transmembrane domains, and the ATP binding site. Of 30 mothers, 23 (76.7%) were carriers. Approximately half of the male siblings of patients with MNK were also diagnosed with MNK . Conclusion Mutations in ATP 7A varied widely across patients, although approximately half of the mutations were located in exons 4, 9, 10, and 15. Approximately 23% of patients did not inherit the mutations from their mothers, but had de novo mutations. An early definite diagnosis is necessary for the early treatment of MNK , and gene analysis serves as an effective method for detecting mutations in ATP 7A .