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.
The frequency of two common disease-associated mutations in the arylsulphatase A (ASA) gene, and of a mutation causing ASA pseudodeficiency, have been established in metachromatic leukodystrophy patients diagnosed in our laboratory.
Analysis on the nucleotide sequence of the ASA genes from another late-infantile MLD patient revealed the presence of a previously unreported G-to-A mutation at the 1,070th nucleotide of the ASA gene (designated 1070A).
A T > C transition causing a Leu > Pro substitution in a conserved region of the arylsulfatase A gene in a late infantile metachromatic leukodystrophy patient.
A 9-bp deletion (2320del9) on the background of the arylsulfatase A pseudodeficiency allele in a metachromatic leukodystrophy patient and in a patient with nonprogressive neurological symptoms.
Molecular genetic characterization of two metachromatic leukodystrophy patients who carry the T799G mutation and show different phenotypes; description of a novel null-type mutation.
The approach used and the results here presented may provide useful information for the study of other MLD patients, as well as new insights about the effect of mutations, such as C300F, in the structure/function of ARSA.
Metachromatic leukodystrophy: subtype genotype/phenotype correlations and identification of novel missense mutations (P148L and P191T) causing the juvenile-onset disease.
In view of the importance of genetic counseling, analyses of mutations and polymorphisms, including the ARSA pseudodeficiency allele, were carried out in 18 unrelated Spanish MLD patients.