Molecular genetic study of Pompe disease in Chinese patients in Taiwan

Pompe disease is caused by mutations in the acid α-glucosidase (GAA) gene. Multiple kinds of mutations in the GAA gene have been reported worldwide. In order to elucidate the molecular basis of the disease in Taiwanese patients of Chinese origin, we have recruited 11 unrelated families who had at least one member with Pompe disease for study. We used 16 pairs of oligonucleotide primers to amplify all the coding regions from exon 2 to 20 in the family members. The coding regions were sequenced on both the sense and antisense strands. We identified 7 different mutations in 17 alleles but failed to identify the defects in the other 5 alleles. The most common defect was D645E (Asp645Glu), accounting for 36% (8/22 alleles) of mutations, followed by G615R (Gly615Arg) (3 alleles); 1411del4 (Glu471-shift) (2 alleles); and one allele each of R600H (Arg600His); ΔN675 (ΔAsn675); 2380delC (Arg794-shift) and 2815delGT (Val939-shift). The molecular defects of POmpe disease are highly heterogeneous in Chinese. Characterization of the molecular defects of the disease is useful for a genotype-phenotype correlation and for genetic counseling and prenatal diagnosis.