ClinVar

Hirschhorn et al. (1994) determined that the common electrophoretic variant of ADA, the ADA2 allozyme (ADA*2), is caused by a 22G-A transition in the ADA gene, resulting in an asp8-to-asn (D8N) substitution. The ADA2 allozyme is a more basic electrophoretic variant that is codominantly inherited with the usual ADA1 allozyme. Functional expression studies of the D8N protein confirmed expression of an enzyme that comigrated with a naturally occurring ADA2 allozyme. Hirschhorn et al. (1994) noted that the ADA2 allozyme has been found in all populations studied and results in only minimally reduced enzyme activity in erythrocytes. The gene frequency of the ADA2 allozyme is estimated as 0.06 in Western populations, lower among individuals of African descent, and higher in Southeast Asian populations. The ADA2 allele was also found on at least 2 different genetic backgrounds, 1 of Ashkenazi Jewish ancestry and 1 in a large Mormon pedigree from Utah, suggesting independent recurrence of the mutation. Consistent with independent recurrence, the G-to-A transition was located in a CpG dinucleotide of the type subject to a high frequency of mutation. Hirschhorn et al. (1994) also found a probable intragenic crossover in the very large first intron that is rich in repetitive DNA sequences.

In 2 Italian groups of autistic children, Bottini et al. (2001) found a significantly higher frequency of the low-activity ADA2 allele than in controls. They suggested that this genotype-dependent reduction in ADA activity may be a risk factor for the development of autism.