title: Sixteen novel mutations in the arylsulfatase A gene causing metachromatic leukodystrophy.
abstract: 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.
authors.affiliation: Lysosomal Diseases Testing Laboratory, Department of Neurology, Thomas Jefferson University, 1020 Locust Street, Room 346, Philadelphia, PA 19107, USA. Electronic address: paola.luzi@jefferson.edu.
authors.forename: Paola
authors.initials: P
authors.lastname: Luzi
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Rafi
authors.forename: Han Zhi
authors.initials: HZ
authors.lastname: Rao
authors.forename: David A
authors.initials: DA
authors.lastname: Wenger
mesh_terms: D000293:Adolescent; D000483:Alleles; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D013433:Sulfoglycosphingolipids / Q000652:urine
chemical_list: D013433:Sulfoglycosphingolipids; D002553:Cerebroside-Sulfatase
keywords: ARSA; Arylsulfatase A; DD; Genotype–phenotype correlations; LI; Lysosomal storage diseases; MLD; MRI; Metachromatic leukodystrophy; PCR; Pd; Sulfatides; WM; arylsulfatase A; developmental delay; late infantile; magnetic resonance imaging; metachromatic leukodystrophy; polymerase chain reaction; pseudodeficiency; white matter