Sixteen novel mutations in the arylsulfatase A gene causing metachromatic leukodystrophy

• Metachromatic leukodystrophy is one of the most common lysosomal storage disorders.
• Mutation analysis was performed in seventy patients affected with MLD.
• Sixteen novel mutations were identified in the arylsulfatase A gene.
• Three other mutations were found previously on a different allelic background.
• Genotype/phenotype correlations were made for the majority of these new mutations.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused mainly by mutations in the arylsulfatase A (ARSA) gene. In this manuscript we report sixteen novel mutations identified in the ARSA gene of fifteen unrelated patients affected with MLD. Of these 16 mutations nine were missense mutations (p.L11Q, p.S44P, p.L81P, p.R84L, p.V177D, p.P284S, p.R288S, p.G301R, p.P425S), three were nonsense mutations (p.Q51X, p.Y149X, p.C156X), three were frame shift mutations (c.28delG, c.105C>A+106_124dup, c.189delC) and one was a splice-site mutation (c.1102-2A>G). In addition, three previously reported mutations were identified on an allelic background different from the one in the original reports. Two mutations, p.G309S and p.E312D, were identified on the background of the so-called pseudodeficiency (Pd) allele while previously they were reported alone. On the other hand, mutation p.R311X was identified in two unrelated patients not in cis with the Pd mutations, as previously reported.