Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy.
To analyze the genetic abnormality in a Japanese patient with adult-type metachromatic leukodystrophy (MLD), we first elucidated the genomic organization of the human arylsulfatase A (ASA) gene and then compared the nucleotide sequences of exons and splice junctions of the mutant ASA gene to those of a normal control. We have identified a new mutation, a G-to-A transition in exon 2, which results in amino acid substitution of Asp for 99Gly. In a transient expression study, COS cells transfected with the mutant cDNA carrying 99Gly----Asp did not show an increase of ASA activity, which confirms that the mutation is a cause of adult-type MLD.
Kondo
R
R
Department of Neurology, Niigata University, Japan.
Wakamatsu
N
N
Yoshino
H
H
Fukuhara
N
N
Miyatake
T
T
Tsuji
S
S
D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*
D002553:Cerebroside-Sulfatase