MOLECULAR ANALYSIS OF GLYCOGEN-STORAGE-DISEASE TYPE IB - IDENTIFICATION OF A PREVALENT MUTATION AMONG JAPANESE PATIENTS AND ASSIGNMENT OF APUTATIVE GLUCOSE-6-PHOSPHATE TRANSLOCASE GENE TO CHROMOSOME-11

Glycogen storage disease type Ib (GSD-Ib) is an inborn error of metabo lism with autosomal recessive inheritance, caused by defects in micros omal transport of glucose-6-phosphate. Recently, Gerin et al isolated a human cDNA encoding a putative transporter homologous to bacterial t ransporters of hexose-6-phosphate, and identified two mutations in its gene in two patients with GSD-Hb (9). Independently, a linkage analys is mapped the GSD-Ib gene on chromosome 11q23 (10). It remains to be e lucidated whether the two genes are identical or GSD-Ib is genetically heterogeneous. We first mapped the transporter gene on chromosome II by using a DNA panel of human/hamster hybridoma cells, The result sugg ested that the GSD-Ib genes identified by the two distinct approaches may be identical and GSD-Ib was allelic, We then studied four unrelate d Japanese families with GSD-Ib, and found three novel mutations: a fo ur-base deletion/two-base insertion, a point mutation within a consens us splicing donor site, and a missense mutation (W118R). The W118R mut ation was found in 4 out of 8 mutant alleles, suggesting that it is pr evalent among Japanese patients. (C) 1998 Academic Press.