Screening for novel mutations in patients with Wilson disease
- Columbia Univ., NY (United States); and others
Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disorder characterized by substantial decrease in biliary excretion of copper and defective incorporation of copper into ceruloplasmin. Affected individuals accumulate high levels of copper in the liver, kidney, and basal ganglia of the brain. The disease results from mutations in the WD gene, a P-type ATPase with six metal binding domains. About 7 novel mutations have been identified which, together, account for roughly half of the population with Wilson disease. Guided by extensive haplotype analysis with six microsatellite markers, we are analyzing unique disease homologues for mutations in all 21 exons with the single-stranded conformational polymorphism (SSCP) protocol. Mobility shifts have indicated putative disease-specific mutations in both intronic and exonic DNA sequence. A reverse dot-blot protocol is being used to evaluate population frequencies of these mutations. We are attempting to correlate the underlying disease mutations with corresponding clinical characteristics, i.e., ceruloplasmin levels, etc. An update of disease gene identification and estimation of disease allele frequencies in diverse populations will be presented.
- OSTI ID:
- 134319
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1052
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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