Identification of novel mutations of the ATP7A gene and prenatal diagnosis of Menkes disease by mutation analysis

ABSTRACT

PURPOSE: Menkes disease is an X-linked recessively inherited disorder caused by the mutation of the ATP7A gene encoding copper-transporting P-type ATPase. The phenotypic features are progressive neurological degeneration, mental retardation, loose skin, and vascular complications. Early diagnosis and treatment are very important for the prognosis of Menkes disease. Here, we describe novel mutations of the ATP7A gene and prenatal diagnosis by mutation analysis. METHODS: Five unrelated Korean Menkes patients were included in this study. They presented with depigmented wool-like hair, progressive neurologic deterioration, and hypotonia in infancy. Serum copper and ceruloplasmin levels were decreased. Brain magnetic resonance imaging revealed tortuous intracranial vessels. Mutation analysis has been carried out using cDNA from cultured skin fibroblasts or genomic DNA from peripheral leukocytes. Prenatal diagnosis was performed in two cases using chorionic villi samples or amniocytes. RESULTS: Four novel mutations have been identified from four different families; c.3511+1GDNA analysis, one was diagnosed as normal, while the other turned out to be a female heterozygote with p.S624_Q724del mutation of the ATP7A gene. CONCLUSION: We identified 4 novel mutations of the ATP7A gene. Prenatal diagnosis in families at risk is critical in order to choose preventive options including an early treatment with copper-histidine therapy or therapeutic termination. Most mutations of the ATP7A gene were frame-shift mutations and prenatal diagnosis has been successfully carried out.