Late-onset metachromatic leukodystrophy: molecular pathology in two siblings.
We report on a new allele at the arylsulfatase A (ARSA) locus causing late-onset metachromatic leukodystrophy (MLD). In that allele arginine84, a residue that is highly conserved in the arylsulfatase gene family, is replaced by glutamine. In contrast to alleles that cause early-onset MLD, the arginine84 to glutamine substitution is associated with some residual ARSA activity. A comparison of genotypes, ARSA activities, and clinical data on 4 individuals carrying the allele of 81 patients with MLD examined, further validates the concept that different degrees of residual ARSA activity are the basis of phenotypical variation in MLD.
Kappler
J
J
Institut für Biochemie 2, Göttingen, Germany.
von Figura
K
K
Gieselmann
V
V
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D001483:Base Sequence; D002553:Cerebroside-Sulfatase / Q000172:deficiency* / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005796:Genes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010641:Phenotype
D002553:Cerebroside-Sulfatase