Prenatal diagnosis and carrier detection for molybdenum cofactor deficiency type A in Northern Israel using polymorphic DNA markers

Molybdenum cofactor deficiency (MoCoD) is an autosomal recessive, fatal neu rological disorder, characterized by the combined deficiency of sulphite ox idase, xanthine dehydrogenase and aldehyde oxidase. We have recently report ed an excessive occurrence of this fatal disorder among segments of the Ara b population in Northern Israel suggesting that the true incidence of MoCoD is probably underestimated in this highly inbred population. This lethal d isease can be diagnosed prenatally by assay of sulphite oxidase activity in chorionic villus samples in pregnancies of couples who have had previously affected children (obligatory carriers). However, to date, there is no bio chemical assay for carrier detection among the population at risk. Recently we demonstrated the linkage of a MoCoD gene to an 8-cM region on chromosom e 6p21.3 in two consanguineous Israeli-Arab unrelated kindreds. The descrip tion of the MOCS1 gene that maps to the same region and which carries multi ple mutations in MoCoD type A followed this finding. We describe here one a dditional kindred of Arab-Israeli origin, which is also linked to the MOCS1 locus, and demonstrate the feasibility of prenatal diagnosis and carrier d etection using microsatellite markers in selected families when mutations a re unknown. A complete correlation between the biochemical and DNA assays w as found in a total of six samples (five chorionic villus and one amniocyte culture sample) obtained from the three MoCoD families. Copyright (C) 2000 John Wiley & Sons, Ltd.