A NEW POLYMORPHISM OF ARYLSULFATASE-A WITHIN THE CODING REGION

A 10-year-old boy with juvenile metachromatic leukodystrophy (MLD) pre sented with the 459 + 1G --> A arylsulfatase A (ASA) mutation on one a llele. To detect his complete genotype, the other ASA allele was seque nced and a T-to-C transition at nucleotide 376 in exon 2 was identifie d. This missense mutation results in a substitution of leucine 76 by p roline. Of 20 MLD unrelated controls, 18 carried the L/P76 mutation ei ther in the homozygous (n = 6) or heterozygous (n = 12) state. The pre sence or absence of L/P76 did not influence leukocyte ASA activity or urinary sulfatide excretion. Apparently, the substitution of leucine 7 6 by proline is a common ASA polymorphism, neither being related to ML D nor creating ASA pseudodeficiency. However, because of its frequency and location, L/P76 may be of particular importance in genetic studie s requiring the differentiation of the ASA alleles within a kindred. F urther studies are directed to the as yet unresolved genotype of the i ndex case with juvenile MLD.