Analysis of two cases of glycogen storage disease type III due to compound heterozygous variants of AGL gene / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To explore the clinical features and genetic basis of two children with glycogen storage disease type III (GSD III).@*METHODS@#The probands and their parents were subjected to genetic testing, and the pathogenity of candidate variants was analyzed by using bioinformatic tools.@*RESULTS@#Sequencing has identified compound heterozygous variants of the AGL gene in both children, namely c.1423+1G>A and c.3701-2A>G in case 1, and c.4213_c.4214insA (p.Glu1405Glufs*17) and c.3589-3C>G in case 2. Both children were diagnosed with GSD III. Literature review suggested that the main type variant among Chinese patients with GSD III involve splice sites of the AGL gene, with c.1735+1G>T being the most common. Based on the American College of Medical Genetics and Genomics standards and guidelines,c.1423+1G>A, c.3701-2A>G and c.4213_c.4214insA variants of AGL gene were predicted to be of pathogenic (PVS1+PM2+PM3, PVS1+PM2+PM3, PVS1+PM2+PP5), and c.3589-3C>G variant was predicted to be of uncertain significance (PM2+PM3+PP3).@*CONCLUSION@#The compound heterozygous variants of the AGL gene probably underlay the GSD III in both children. Above findings have enriched the spectrum of genetic variants underlying this disease.