title: Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein.
abstract: 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.
authors: ICRF Laboratories, John Radcliffe Hospital, Headington, Oxford, UK.
authors: J
authors: J
authors: Chelly
authors: Z
authors: Z
authors: Tümer
authors: T
authors: T
authors: Tønnesen
authors: A
authors: A
authors: Petterson
authors: Y
authors: Y
authors: Ishikawa-Brush
authors: N
authors: N
authors: Tommerup
authors: N
authors: N
authors: Horn
authors: A P
authors: AP
authors: Monaco
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000073840:Copper-Transporting ATPases; D004247:DNA; D005260:Female; D006801:Humans; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics*; D008670:Metals / Q000378:metabolism*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D014960:X Chromosome
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008670:Metals; D011993:Recombinant Fusion Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases