title: A novel homozygous mutation at the GAA gene in Mexicans with early-onset Pompe disease.
abstract: Glycogen-storage disease type II, also named Pompe disease, is caused by the deficiency of the enzyme acid alpha-glucosidase, which originates lysosomal glycogen accumulation leading to progressive neuromuscular damage. Early-onset Pompe disease shows a debilitating and frequently fulminating course. To date, more than 300 mutations have been described; the majority of them are unique to each affected individual. Most early-onset phenotypes are associated with frameshift mutations leading to a truncated alpha-glucosidase protein with loss of function. Founder effects are responsible from many cases from few highprevalence world regions. Herein we described two apparently unrelated cases affected with classical early-onset Pompe disease, both pertaining to a small region from Central Mexico (the State of San Luis Potosí), the same novel homozygous frameshift mutation at gene GAA (c.1987delC) was demonstrated in both cases. This GAA gene deletion implies a change of glutamine to serine at codon 663, and a new reading frame that ends after 33 base pairs, which leads to the translation of a truncated protein. This report contributes to widen the knowledge on the effect of pathogenic mutations in Pompe disease. Here we postulate the existence of a founder effect.
authors.affiliation: Department of Genetics, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, México; ; School of Medicine, Universidad Cuauhtémoc, San Luis Potosí, México;
authors.forename: Carmen
authors.initials: C
authors.lastname: Esmer
authors.affiliation: Department of Pediatric Cardiology, Hospital Central "Dr. Ignacio Morones Prieto, San Luís Potosí, México;
authors.forename: Rosario
authors.initials: R
authors.lastname: Becerra-Becerra
authors.affiliation: Department of Pathology, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, México;
authors.forename: Claudia
authors.initials: C
authors.lastname: Peña-Zepeda
authors.affiliation: Department of Neuropediatrics, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, México.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bravo-Oro
mesh_terms: D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology; D017809:Fatal Outcome; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008800:Mexico; D009154:Mutation; D011859:Radiography; D000520:alpha-Glucosidases / Q000172:deficiency / Q000235:genetics
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases
keywords: Acid maltase deficiency; Early-onset Pompe disease; Founder effect