2 NOVEL MUTATIONS IN A JAPANESE PATIENT WITH THE LATE-INFANTILE FORM OF METACHROMATIC LEUKODYSTROPHY

Two novel mutations in the arylsulfatase A (ASA) gene from a Japanese patient with the late-infantile form of metachromatic leukodystrophy ( MLD) were identified, One mutation was a G to C transversion at nucleo tide 608 of the ASA gene (designated 608C) located at the 3' end of ex on 2, which resulted in an amino acid substitution of Gin 153 to His, Although the 608 mutation resulted in a change in the exon-intron boun dary consensus sequence, analysis of cDNA from the patient did not rev eal the presence of aberrant splicing, The second mutation, a G to T t ransversion at nucleotide 1572 in exon 5 (designated 1572T), resulted in an amino acid substitution of Gly 308 to Val, This could potentiall y result in a conformational change in ASA protein structure. The pati ent was heterozygous for these two new mutations which were not presen t in 18 Japanese MLD alleles examined, A transient expression study in COS-1 cells showed no residual activity in either mutation, These res ults indicate that the 608C and 1572T mutations are responsible for th e occurrence of the late-infantile form of MLD.