A SINGLE ORIGIN FOR THE MOST FREQUENT MUTATION CAUSING LATE INFANTILEMETACHROMATIC LEUKODYSTROPHY

Metachromatic leucodystrophy is an autosomal recessive degenerative di sease of the nervous system caused by the deficiency of the lysosomal enzyme arylsulphatase A (ARSA). We report here on the high incidence o f late infantile MLD among Muslim Arabs originating from Jerusalem, mo st probably because of a founder effect. All the patients were found t o be homozygous for 459 + 1 G --> A, a mutation which destroys the spl ice donor site of exon 2 of the ARSA gene. This mutation has been repo rted to be the most common mutation causing MLD. We studied the ARSA h aplotype defined by three intragenic polymorphic sites in DNA samples from Muslim Arab patients from Jerusalem, a Christian Arab patient ori ginating from the region, and eight other white patients, all homozygo us for the 459 + 1 G --> A mutation. Ah the alleles carried the same h aplotype which is in complete linkage disequilibrium with the mutation . This finding indicates a common origin for the 459 + 1 G --> A mutat ion which may have been introduced into Jerusalem at the time of the C rusades.