title: Novel mutations in arylsulfatase A gene in three Ukrainian families with metachromatic leukodystrophy.
abstract: Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the deficiency of arylsulfatase A (ARSA) or saposin B. The majority of mutations identified in patients with MLD are unique within individual families. Here, we report on the novel missense mutations (F247S, D381E, and A469G) and the known mutations "A" allele and P136S in the ARSA gene in three unrelated Ukrainian families with MLD. The mutations F247S and P136S were found in compound heterozygous with the "A" allele in two patients with juvenile onset MLD. The clinical features of the typical patient with genotype D381E/A469G (early onset with very rapid manifestation of disease) suggest the reason to distinguish an early infantile MLD variant.
authors.affiliation: Department of Medical Genetics, Kyiv Medical Academy of Postdiploma Education, Kyiv, Ukraine.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Olkhovich
authors.forename: Noboru
authors.initials: N
authors.lastname: Takamura
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Pichkur
authors.forename: Natalia G
authors.initials: NG
authors.lastname: Gorovenko
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002553:Cerebroside-Sulfatase / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007966:Leukodystrophy, Metachromatic / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D013433:Sulfoglycosphingolipids / Q000652:urine; D014455:Ukraine / Q000453:epidemiology
chemical_list: D013433:Sulfoglycosphingolipids; D002553:Cerebroside-Sulfatase