Nature Genetics
3, 14 - 19 (1993)
doi:10.1038/ng0193-14
Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding proteinJamel Chelly1, Zeynep Tümer2, Tønne Tønnesen2, Anne Petterson2, Yumiko Ishikawa-Brush1, Niels Tommerup2, Nina Horn2
& Anthony P. Monaco1
1ICRF Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital Headington, Oxford OX3 9DU, UK
2The John F. Kennedy Institute and The Danish Center for Human Genome Research, Gl.Landevej 7, 2600 Glostrup, Denmark Correspondence should be addressed to A.P.M. Menkes disease is a lethal−X linked recessive disorder associated with copper metabolism disturbance. We have recently mapped two chromosome breakpoints related to this disease in a 1 megabase yeast artificial chromosome contig at Xq13.3. We now report the construction of a phage contig and the isolation of candidate partial cDNAs for the Menkes disease gene. The candidate gene expresses an 8 kb message in all investigated tissues, and deletions were detected in 16% of 100 unrelated Menkes patients. The deduced partial protein sequence shared the GMTCXXC motif with bacterial metal resistance operons, suggesting a potential heavy metal binding protein. These findings should lead to more accurate prenatal diagnosis of this severe disease and a better understanding of the cellular homeostasis of essential heavy metals.
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