Metachromatic leukodystrophy: identification of the first deletion in exon 1 and of nine novel point mutations in the arylsulfatase A gene.
Hum Mutat
; 9(3): 234-42, 1997.
Article
em En
| MEDLINE
| ID: mdl-9090526
ABSTRACT
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 + 1G-->A 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 + 1G-->A, 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cerebrosídeo Sulfatase
/
Leucodistrofia Metacromática
/
Mutação
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Mutat
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
França