Springer Online Journal Archives 1860-2000
Abstract Molybdenum cofactor (MoCo) deficiency is a rare and devastating disease resulting in neonatal seizures and other neurological symptoms identical to those of sulphite oxidase deficiency. It is an autosomal recessive disease and no therapy is known. Most patients harbour MOCS1 mutations, which are found in both open reading frames of this unusual gene encoding the first two enzymes required in the MoCo biosynthesis pathway, MOCS1 A and MOCS1 B, in a single transcript. We describe genomic details as a prerequisite for comprehensive mutation analysis. In an initial cohort of 24 MoCo deficiency patients, we identified 13 different mutations on 34 chromosomes, with a mutation detection rate of 70%. Five mutations were observed in more than one patient and together accounted for two thirds of detected mutations. These comprise the most frequent mutation, R319Q, which is restricted to England, two Danish/German mutations (one missense and one splice site mutation), a missense mutation found in England and Germany, and a “Mediterranean” frameshift mutation. All patients with identified mutations are either homozygous or compound heterozygous for mutations in either of the two open reading frames corresponding to MOCS1 A and MOCS1 B, respectively. This observation suggests the existence of more than the two previously described complementation groups in MoCo biosynthesis.
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