Population frequency of the arylsulphatase A pseudo-deficiency allele
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The enzymatic diagnosis of metachromatic leukodystrophy is complicated by the frequent occurrence of the pseudo-deficiency of arylsulphatase A (ASA) enzyme activity. An A to G nucleotide transition in the first polyadenylation signal of the ASA gene results in the loss of its major mRNA species and a greatly reduced level of enzyme activity. This nucleotide change (nucleotide 1620 of the ASA cDNA) is the cause of ASA pseudo-deficiency and is closely linked to another A to G transition (nucleotide 1049), within the ASA gene, which changes Asn350 to serine but which does not affect ASA activity. The distribution of these 2 nucleotide changes has been investigated in 73 unrelated individuals from the Australian population. The two transitions were found together on 14 (9.6%) out of 146 chromosomes. The transition at nucleotide 1620 was not found alone; however, the other transition was found alone on 7 (4.8%) out of the 146 chromosomes. The carrier frequency of the ASA pseudo-deficiency mutation in Australia is thus estimated to be about 20%.
KeywordsNucleotide Enzyme Activity Serine Metabolic Disease Frequent Occurrence
- Dubois G, Turpin J-C, Baumann N (1975) Absence of ASA activity in healthy father of a patient with metachromatic leukodystrophy. N Engl J Med 293:302Google Scholar
- Kolodny EH (1989) Metachromatic leukodystrophy and multiple ulfatase deficiency: sulfatide lipidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 1721–1750Google Scholar
- Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NYGoogle Scholar