IDENTIFICATION OF AN E689K SUBSTITUTION AS THE MOLECULAR-BASIS OF THEHUMAN ACID ALPHA-GLUCOSIDASE TYPE-4 ALLOZYME (GAA-ASTERISK-4)

We have identified the molecular basis of the GAA4 allozyme as a G to A transition at nt2065 which predicts the substitution of glutamic ac id by lysine at codon 689 (E689K). The conclusion that this change rep resents the molecular basis of the GAA4 allozyme is based on 1) prese nce of the G2065A in homozygosity in a known GAA4 homozygote, 2) tran sient expression studies showing normal enzyme activity expressed by c DNA containing the G2065A transition and 3) isoelectric focusing studi es showing a more cathodal pattern for the expressed product as compar ed to the common GAA1, analogous to the patterns seen in normal and k nown GAA4 lymphoid cells.