Screening for novel mutations in patients with Wilson disease

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134319

Shah, A B; Petrukhin, K; Chernov, I ^[1]

---

1. 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--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ATP-ASE
BIOLOGICAL MARKERS
COPPER
CORRELATIONS
DIGESTIVE SYSTEM DISEASES
DNA SEQUENCING
EXONS
GENE MUTATIONS
GENES
HEREDITARY DISEASES
INTRONS
METABOLIC DISEASES
METABOLISM
MUTATION FREQUENCY
PATIENTS
PHENOTYPE
RECESSIVE MUTATIONS