Genetic analysis of 76 Spanish Pompe disease patients: Identification of 12 novel pathogenic GAA variants and functional characterization of splicing variants

Gene. 2022 Jan 15;808:145967. doi: 10.1016/j.gene.2021.145967.

PMID: 34530085

Cinthia Amiñoso, Jesús Solera

Highlights: In this study, 76 Spanish patients are reported with either infantile or late onset form of Pompe disease. Functional characterization of some splice mutations showed deleterious mechanisms on the processing of mRNA.

Abstract

Background: Glycogenosis type II (GSDII), also known as Pompe disease (MIM 232300), is an autosomal recessive condition caused by a lysosomal acid-glucosidase deficiency. Normal enzyme synthesis is disrupted by mutations in the GAA gene, which leads to the accumulation of intralysosomal glycogen, which is important for the severity and course of the disease.

Objective and methods: The results of a study of 76 patients from Spain who had either an infantile or a lateonset form of Pompe disease are presented in this study. The study focused on the exons and intron flanking fragments of the GAA gene on a molecular level.

Results and conclusion: 55 distinct molecular pathogenic variants were found, 12 of which had never been seen before. In addition, it was discovered that the c.-32-13T>G mutation is present in 84.37% of patients with the late-onset form of the disease. The functional characterization of several splice mutations revealed that they have deleterious effects on mRNA processing.

Keywords: Aberrant splicing, Functional characterization, Genetic analysis, Pompe disease