title: Localization of a gene for molybdenum cofactor deficiency, on the short arm of chromosome 6, by homozygosity mapping.
abstract: Molybdenum cofactor deficiency (MoCoD) is a fatal disorder manifesting, shortly after birth, with profound neurological abnormalities, mental retardation, and severe seizures unresponsive to any therapy. The disease is a monogenic, autosomal recessive disorder, and the existence of at least two complementation groups suggests genetic heterogeneity. In humans, MoCoD leads to the combined deficient activities of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. By using homozygosity mapping and two consanguineous affected kindreds of Israeli-Arab origin, including five patients, we demonstrated linkage of a MoCoD gene to an 8-cM region on chromosome 6p21.3, between markers D6S1641 and D6S1672. Linkage analysis generated the highest combined LOD-score value, 3.6, at a recombination fraction of 0, with marker D6S1575. These results now can be used to perform prenatal diagnosis with microsatellite markers. They also provide the only tool for carrier detection of this fatal disorder.
authors.affiliation: Department of Genetics, Tamkin Human Molecular Genetics Research Facility, Technion-Israel Intitute of Technology, Bruce Rappaport Faculty of Medicine, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Shalata
authors.forename: H
authors.initials: H
authors.lastname: Mandel
authors.forename: J
authors.initials: J
authors.lastname: Reiss
authors.forename: R
authors.initials: R
authors.lastname: Szargel
authors.forename: A
authors.initials: A
authors.lastname: Cohen-Akenine
authors.forename: C
authors.initials: C
authors.lastname: Dorche
authors.forename: M T
authors.initials: MT
authors.lastname: Zabot
authors.forename: A
authors.initials: A
authors.lastname: Van Gennip
authors.forename: N
authors.initials: N
authors.lastname: Abeling
authors.forename: M
authors.initials: M
authors.lastname: Berant
authors.forename: N
authors.initials: N
authors.lastname: Cohen
mesh_terms: D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000172:deficiency / Q000235:genetics; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003067:Coenzymes / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D008667:Metalloproteins / Q000494:pharmacology*; D018895:Microsatellite Repeats / Q000235:genetics; D000090006:Molybdenum Cofactors; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000172:deficiency* / Q000235:genetics; D010375:Pedigree; D011296:Prenatal Diagnosis; D011621:Pteridines / Q000494:pharmacology*; D014968:Xanthine Dehydrogenase / Q000172:deficiency / Q000235:genetics
chemical_list: D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases; D003067:Coenzymes; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011621:Pteridines; D014968:Xanthine Dehydrogenase; C022261:molybdopterin