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., Wakamatsu, N., Yoshino, H., Fukuhara, N., Miyatake, T., & Tsuji, S. (1991). Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy. American Journal of Human Genetics, 48(5), 971–978.