IJMDC. 2022; 6(6): 864-874

Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease

Authors: Aly Ezzat, Marwan El Bagoury, Sherif Roushdy, Yahia Aktham.

ABSTRACT

Fabry disease (FD) is a rare, progressive, inherited disorder resulting from a markedly deficient enzyme activity of α-galactosidase A (AGAL), which is caused by mutations in the X-linked α-galactosidase A (GLA) gene. FD is perceived as a multidomain or a heterogeneous disease phenotype associated with complex pathophysiological manifestations and cascading pathways. The AGAL activity accurately predicts the severity of FD. It is vital to study the variants related to FD in the Gulf region because the existing population is mixed, and a founder gene, if predominant in any generation, leads to greater birth rates of autosomal recessive disorders. Identifying the pathogenicity of GLA mutations plays a crucial role in diagnosing and treating FD. We conducted an extensive review of the literature. We pooled data from randomized controlled trials, retrospective observational trials, systematic reviews, and case reports on p.D313Y variant pathogenicity versus nonpathogenicity and clinical significance for establishing genotype-phenotype correlations in patients with suspected FD. Overall, in our review analysis, we included 25 studies. Data on study participants, type of mutation, clinical manifestations, and clinical relevance were collected. Interestingly, we found strong evidence reporting nonpathogenicity of the D313Y variant and categorized it as benign or a variant of uncertain significance. These results will facilitate the clinicians to decide on the correct diagnosis and treatment of FD. Further research is warranted, which would help clarify a possible relationship between the variant and clinical manifestations.

Keywords:
Fabry disease, p.D313Y, α-galactosidase A, GLA variants, pathogenic variants, variant of unknown significance


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Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease


Authors
Aly Ezzat
Medical Affairs Department, Sanofi-Genzyme, Gulf region
PubMed articlesGoogle scholar articles

Marwan El Bagoury
Medical Affairs Department, Sanofi-Genzyme, Gulf region
PubMed articlesGoogle scholar articles

Sherif Roushdy
Medical Affairs Department, Sanofi-Genzyme, Gulf region
PubMed articlesGoogle scholar articles

Yahia Aktham
Medical Affairs Department, Sanofi-Genzyme, Gulf region.
PubMed articlesGoogle scholar articles


Correspondence to:
. Yahia Aktham, Medical Affairs Department, Sanofi-Genzyme, Gulf region.; Yahia.Aktham@sanofi.com

Publication history
Received 10 Nov 2021
Revised 21 Mar 2022
Accepted 20 Apr 2022
Published online 18 May 2022
Published in print 04 Jun 2022

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Pubmed Style

Ezzat A, Bagoury ME, Roushdy S, Aktham Y. Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease. IJMDC. 2022; 6(6): 864-874. doi:10.24911/IJMDC.51-1634565050


Web Style

Ezzat A, Bagoury ME, Roushdy S, Aktham Y. Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease. https://www.ijmdc.com/?mno=133962 [Access: August 18, 2022]. doi:10.24911/IJMDC.51-1634565050


AMA (American Medical Association) Style

Ezzat A, Bagoury ME, Roushdy S, Aktham Y. Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease. IJMDC. 2022; 6(6): 864-874. doi:10.24911/IJMDC.51-1634565050


Vancouver/ICMJE Style

Ezzat A, Bagoury ME, Roushdy S, Aktham Y. Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease. IJMDC. (2022), [cited August 18, 2022]; 6(6): 864-874. doi:10.24911/IJMDC.51-1634565050


Harvard Style

Ezzat, A., Bagoury, . M. E., Roushdy, . S. & Aktham, . Y. (2022) Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease. IJMDC, 6 (6), 864-874. doi:10.24911/IJMDC.51-1634565050


Turabian Style

Ezzat, Aly, Marwan El Bagoury, Sherif Roushdy, and Yahia Aktham. 2022. Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease. International Journal of Medicine in Developing Countries, 6 (6), 864-874. doi:10.24911/IJMDC.51-1634565050


Chicago Style

Ezzat, Aly, Marwan El Bagoury, Sherif Roushdy, and Yahia Aktham. "Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease." International Journal of Medicine in Developing Countries 6 (2022), 864-874. doi:10.24911/IJMDC.51-1634565050


MLA (The Modern Language Association) Style

Ezzat, Aly, Marwan El Bagoury, Sherif Roushdy, and Yahia Aktham. "Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease." International Journal of Medicine in Developing Countries 6.6 (2022), 864-874. Print. doi:10.24911/IJMDC.51-1634565050


APA (American Psychological Association) Style

Ezzat, A., Bagoury, . M. E., Roushdy, . S. & Aktham, . Y. (2022) Understanding the pathogenic and nonpathogenic mutations and implications of α-galactosidase variant D313Y in Fabry disease. International Journal of Medicine in Developing Countries, 6 (6), 864-874. doi:10.24911/IJMDC.51-1634565050


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