Variable Genotype–Phenotype Correlation of Pompe's Disease Caused by a c.2015 G > A (p.Arg672Gln) Mutation in the GAA Gene

Abstract

Pompe's disease occurs due to an autosomal recessive trait resulting from numerous distinctive mutations in the GAA gene. It manifests as a broad spectrum of clinical phenotypes with progressive weakness that impairs motor and respiratory functions being common for all its forms. Cardiac hypertrophy is a prominent feature of its classic infantile form. To date, the pathogenic variant c.2015G > A (p.Arg672Gln) in exon 14 of the GAA gene has been described in 10 children of different ethnic groups, with variable phenotypic presentations. This work describes three children from two unrelated families of Arab ethnicity who presented with infantile-onset Pompe's disease as a result of a c.2015G > A (p.Arg672Gln) mutation. The clinical course of the children we report was more severe than previous reports. This further emphasizes the lack of a strict genotype–phenotype correlation in regard to the unique c.2015G > A (p.R672Q) mutation that causes Pompe's disease. This information contributes to the knowledge of the phenotypic expression of the specific mutation c.2015G > A (p.Arg672Gln) that causes Pompe's disease.

Keywords

Pompe's disease - genetic - genotype–phenotype - mutation - variant - children

Declaration of Patient Consent

The authors certify that they have obtained signed consent forms from the legal guardians of the patients presented in this report, who have agreed for the clinical information of the patients to be published. The patient's guardians understand that while the names and initials of the patients will not be published and that all efforts will be made to conceal their identity; their anonymity cannot be guaranteed.

Ethical Publication

We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Publication History

Received: 16 July 2020

Accepted: 01 November 2020

Article published online:
12 February 2021

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