The identification of five novel mutations in the lysosomal acid a‐(1,4) glucosidase gene from patients with glycogen storage disease type II

Abstract

The autosomal recessive disorder Glycogen Storage Disease Type II (GSDII) is caused by a deficiency in the lysosomal enzyme acid α-glucosidase. We have optimised a procedure to use fluorescent DNA sequencing technology to screen for mutations within the α-glucosidase gene from UK patients with GSDII. Five previously unknown mutations in six patients (4 early onset infantile and 2 late onset adult) have been found. The mutations are an insertion of a C residue in exon 2 (InsC258), an insertion of a G residue in exon 16 (InsG2242), a deletion of 20 nucleotides in exon 4 Δ, and a nonsense mutation in exon 16 (G2237A - Trp746Stop). All will result in the introduction of a premature stop codon in the coding region, predicting a truncated and non-functional protein. The final mutation is a duplication of 18 nucleotides in exon 19 (Ins18nt2776) and will result in the insertion of an additional six amino acids into the protein chain after Asn925 (Gly-Val-Pro-Val-Ser-Asn). Hum Mutat 11:413, 1998. © 1998 Wiley-Liss, Inc.