ARSA gene mutations in five Chinese metachromatic leukodystrophy patients.

The objective was to identify arylsulfatase A mutations, if any, in five Chinese patients with metachromatic leukodystrophy. This would be the first such study in China. All eight exons and exon-intron boundaries of the arylsulfatase A gene (ARSA) were amplified with polymerase chain reaction, which was followed by direct DNA sequencing. Patient 1 exhibited a homozygous mutation at c.954G>A (p.W318X) in exon 5. Patient 2 exhibited compound heterozygous mutations, identified as one allele with the c.862C>T (p.R288C) missense mutation in exon 5 and the other allele with the c.1338dupC frameshift mutation in exon 8. Patient 3 exhibited only a c.179_180dupCA frameshift mutation in exon 1 in one allele. Patients 4 and 5 exhibited identical compound heterozygous mutations, identified as one allele with the c.296G>T (p.G99V) missense mutation and the other allele with the c.251G>A (p.R84Q) missense mutation in exon 2. Six DNA variants of the arylsulfatase A gene were identified: two novel frameshift mutations (c.179_180dupCA and c.1338dupC), one known nonsense mutation (p.W318X), and three known missense mutations (p.R84Q, p.G99V, and p.R288C).