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Metachromatic leukodystrophy: Identification of the first deletion in exon 1 and nine novel point mutations in the arylsulfatase A gene

✍ Scribed by Ruxandra Draghia; Franck Letourneur; Cristina Drugan; Jeanne Manicom; Christophe Blanchot; Axel Kahn; Livia Poenaru; Catherine Caillaud

Publisher: John Wiley and Sons
Year: 1997
Tongue: English
Weight: 273 KB
Volume: 9
Category: Article
ISSN: 1059-7794
DOI: 10.1002/(sici)1098-1004(1997)9:3<234::aid-humu4>3.0.co;2-7

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✦ Synopsis

Metachromatic leukodystrophy (MLD), a lysosomal storage disease caused by the deficiency of arylsulfatase A (ASA), is inherited as an autosomal recessive trait, and its frequency is estimated to be 1 in 40,000 live births. Genomic DNA from 21 MLD patients (14 late-infantile and 7 juvenile cases) was amplified in four overlapping PCR fragments and tested by allele-specific oligonucleotide (ASO) for the two common mutations 459 + lGÃA and P426L. These mutations were found in only 28.6% of the alleles studied. The remaining alleles were analyzed by chemical mismatch cleavage (CMC and automatic sequencing. In addition to five previously reported mutations (459 + lGÃA, A212V, R244C, R390W, P426L), 10 novel mutations were identified: 9 missense mutations (S95N, G119R, D152Y, R244H, S250Y, A314T, R384C, R496H, K367N) and one 8 bp deletion in exon 1, the first mutation reported in this exon. These methods allowed us to identify 76% of the alleles tested. Genotype-phenotype correlations could be established for some of these mutations. These results confirm the heterogeneity of mutations causing MLD and suggest that CMC is a reliable and informative screening method for point mutation detection in the arylsulfatase A gene. Hum

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