LOCALIZATION OF A GENE FOR MOLYBDENUM COFACTOR DEFICIENCY, ON THE SHORT ARM OF CHROMOSOME-6, BY HOMOZYGOSITY MAPPING

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 dis ease is a monogenic, autosomal recessive disorder, and the existence o f 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 homoz ygosity mapping and two consanguineous affected kindreds of Israeli-Ar ab 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. Th ese results now can be used to perform prenatal diagnosis with microsa tellite markers. They also provide the only tool for carrier detection of this fatal disorder.