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Phenotypic consequences of GBA1 pathological variant R463C (p.R502C)
Emory Ryan1, Samantha Nishimura1, Grisel Lopez1
1National Human Genome Research Institute, National Institutes of Health, Bethesda, USA.
Gaucher disease (GD) phenotypes vary widely, even with the R463C GBA1 variant. This study highlights the need for long-term patient monitoring to understand symptom development and neurological involvement in Gaucher disease.
Area of Science:
- Genetics and Genomics
- Lysosomal Storage Disorders
- Rare Diseases
Background:
- Gaucher disease (GD) is an inherited lysosomal storage disorder.
- Pathological variants in the GBA1 gene cause GD.
- Phenotypic variability complicates genotype-based predictions.
Purpose of the Study:
- To investigate the clinical spectrum of Gaucher disease associated with the R463C GBA1 variant.
- To analyze patient data from the National Institutes of Health (NIH) and published literature.
Main Methods:
- Retrospective review of 25 NIH patient records.
- Systematic literature search of PubMed and Web of Science (up to December 2023).
- Analysis of GBA1 genotypes and associated Gaucher disease phenotypes.
Main Results:
- The R463C variant was found in patients with GD1 and GD3 classifications.
- Common second variants with R463C included N370S and L444P.
- Phenotypes often correlated with the second GBA1 variant, but showed significant diversity.
Conclusions:
- The R463C GBA1 variant is associated with a broad spectrum of Gaucher disease phenotypes.
- Phenotypic expression is influenced by the second GBA1 allele.
- Longitudinal follow-up is crucial for Gaucher disease management and understanding GBA1 variant effects.
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