Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menkes disease (MNK) lies immediately proximal to pphosphoglycerate kinase (PGK1) in Xq13 in human. Phenotypic similarities between MNK patients and murine mottled (Mo) mutants strongly suggest that both defects are caused by mutations at the same locus. Human MNK cDNA clones and a genomic subclone derived from a 40-kb YAC clone that includes Pgk1 have been used to position the murine homologue of Menkes disease (MNK, Mnk) immediately proximal to, and within 150-200 kb of, phosphoglycerate kinase (Pgk1) on the mouse X chromosome using interspecific backcross analysis and pulsed-field gel electrophoresis. A related autosomal locus has been mapped to mouse chromosome 18. RFLVs at Mnk between inbred strains of mice that show a strong association with the presence of the Mo phenotype have been detected. Hybridization of 4.1 kb of the 4.5-kb MNK coding sequence failed to reveal any deletions or alterations to restriction fragments containing exons of the Mnk locus in 9 Mo mutants. Furthermore, no genomic deletions or alterations > 20 kb were detected in 10 independently derived Mo mutants using pulsed-field gel electrophoresis. As no deletions or alterations at the Mnk gene were found, we suggest that any mutations in Mnk that cause the Mo phenotype are likely to be due to small changes at the nucleotide level and/or small deletions (< 20 kb) that lie outside the coding sequence.
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PMID:Analysis of Mnk, the murine homologue of the locus for Menkes disease, in normal and mottled (Mo) mice. 795 88

Menkes disease is an X-linked recessive disorder of copper metabolism resulting in death in early infancy. The gene has been mapped to band Xq13 based, in part, on a translocation breakpoint in a female with the disease, which was found to lie within 300 kilobases (kb) of the PGK-1 locus, allowing the isolation of a YAC clone spanning the breakpoint. Phage subclones from the breakpoint region were isolated and used to screen cDNA libraries. cDNA clones were found which detect an 8 kb transcript from normal individuals but show diminished or absent hybridization in Menkes disease patients. Partial sequence of the cDNA shows a unique open reading frame containing putative metal binding motifs which have been found in heavy metal resistance genes in bacteria. This gene is a strong candidate for the Menkes disease gene.
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PMID:Isolation of a partial candidate gene for Menkes disease by positional cloning. 849 Jun 49