Molecular pathology of copper metabolism: Mutation screening in the ATP7A gene in Czech patients with Menkes disease ‐ identification of two novel mutations

• Published in: The FASEB journal 2006-03, Vol.20 (4), p.A98-A98
• Main Authors: Kralik, Lubomir, Flachsova, Eva, Zeman, Jiri, Martasek, Pavel
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.4.A98

Menkes disease is one of the inborn disorders of copper metabolism. It is an X‐linked recessive disease caused by a defect in the Menkes (ATP7A) gene which spans about 140 kb of genomic DNA and contains 23 exons that encode a 1500 amino acid long transmembrane copper‐transporting P‐type ATPase. Affected males suffer from a systemic copper deficiency due to malabsorption and defective distribution of dietary copper resulting in a connective‐tissue disturbance and profound neurodegeneration in early childhood. In this study, a mutational analysis of patients with Menkes disease from Czech Republic was performed. Genomic DNA of three unrelated patients with Menkes disease was investigated for mutations in the ATP7A gene using a direct sequencing method of all 23 exons amplified by PCR. The restriction fragment length polymorphism assay was established for each identified mutation. Three nonsense mutations were found in the ATP7A gene: Q724X, E1249X and Q1288X. The two mutation Q724X and E1249X were not previously published. These mutations are predicted to result in the premature termination of the protein. The present findings not only helps us in understanding the underlying genetic defect but are invaluable data especially for carrier detection and prenatal diagnosis of this lethal disorder. (Supported by grant MSM 0021620806)