Finnish-Type Aspartyiglucosaminuria Detected by Oligonucleotide Ligation Assay

Aspartyiglycosaminuria (AGU) is a recessively inherited lysosomal storage disease that occurs with much higher frequency in Finlandthan elsewhere. AGU is caused by a deficiency in glycosylasparaginase (GA), which results in the accumulation of glycoasparagines in lysosomes. In the Finnish population, a single nucleotide change in the gene encoding GA is responsible for the disease. We have used the oligonucleotide ligation assay (OLA) to detect the mutation in polymerase chain reaction (PCR)-amplified DNA samples from normal, carrier, and affected individuals. Screening for AGU among 415 random Finn-ish DNA samples with PCR/OLA revealed five carriers of the mutant allele and demonstrated the potential of the method for use in carrier screening. PCR/OLA provides a rapid, reliable, nonisotopicmethod to detect the mutation responsible for AGU that can readily be applied to large population screening. Indexing Terms: lysosomal storage disease/population screen-ing/gene mutations Aspartylglycosaminuria (AGU) is an autosomal reces-sive disorder characterized by serious psychomotor retar-dation.4 It arises from the accumulation of aspartyiglu-cosamine as a result of incomplete catabolism of asparagine-linked glycoproteins in lysosomes (1, 2). The incidence of this disease outside Finland is very low but in northern and eastern Finland it is estimated to affect between 1 in 4000 and 1 in 7000 individuals, with a carrie