MISSENSE MUTATIONS IN THE ARYLSULFATASE-A GENES OF METACHROMATIC LEUKODYSTROPHY PATIENTS

Novel predicted disease-causing mutations have been defined in three p atients with metachromatic leukodystrophy (MLD). The first new mutatio n is a C-->A change at base 884 in exon 5 of the arylsulphatase A (ASA ) gene causing a serine to tyrosine substitution at position 295 of th e protein (S295Y). A late-infantile MLD patient was found to be homozy gous for this mutation. The second mutation is a G-->A substitution at nucleotide 1144 in exon 7, that causes a glutamic acid to lysine subs titution at amino acid 382 (E382K). A juvenile MLD patient was found t o be homozygous for this mutation. Finally an adult MLD patient has be en shown to be heterozygous for two novel point mutations in exon 3. T hese are both C-->T changes at position 635 and 671 that result in ala nine to valine substitutions at amino acids 212 (A212V) and 224 (A224V ) of the ASA protein.