Identification of four novel mutations in classical Menkes disease and successful prenatal DNA diagnosis

Menkes disease is an X-linked recessive disorder of the copper metabolism and affected males suffer a systemic copper deficiency due to malabsorption and defective distribution of dietary copper. It is caused by a defect in the Menkes (ATP7A) gene, which encodes a transmembrane copper-transporting P-type ATPase. A variety of mutations were reported; however, only a few mutations were reported in Asian patients. We identified four novel mutations and one known mutation in five Korean patients. Arg646Ter in exon 8, a novel mutation transmitted from his carrier mother, was identified in one patient. Prenatal DNA diagnosis on an unaffected fetus in this carrier mother was successfully accomplished. An additional three novel mutations, Leu706Arg in exon 9, Gly1118Asp in exon 17, and Gly1255Arg in exon 19, were identified. Splicing mutation was not identified. Menkes disease in Korean patients appears to be caused by heterogeneous mutations with different spectrums from Caucasian patients.