The Importance of Genetic Diagnostic Modalities in Gaucher Disease
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Abstract
Gaucher disease (GD) is a rare lysosomal storage disorder due to a deficiency in the enzyme acid β-glucosidase (GCase), which leads to the accumulation of glucosylceramide in various body tissues. This autosomal recessive disorder is primarily associated with pathogenic variants in the GBA1 gene. Accurate and timely diagnosis of GD is essential for effective management and treatment. This article reviews the role of genetic diagnostic modalities in diagnosing GD, highlighting recent advancements and their clinical implications. Various genetic testing techniques, including Sanger sequencing, next-generation sequencing (NGS), and single molecule real-time (SMRT) sequencing are discussed in this article. Each method offers unique advantages and challenges, particularly in distinguishing between the GBA1 gene and its pseudo-gene. The clinical utility of genetic testing extends to early diagnosis and treatment initiation, risk assessment, and guiding therapeutic decisions based on specific GBA1 variants. Challenges such as the complexity of the GBA1 gene, the classification of variants of uncertain significance (VUS), and ethical considerations are also addressed in this study. Ongoing research and advancements in genetic testing technologies aim to improve the accuracy, accessibility, and clinical utility of genetic testing for GD. This review underscores the importance of genetic diagnostic modalities in comprehensive management of Gaucher disease.
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