GBA Mutation Assay Service

Our cutting-edge GBA mutation assay service provides unparalleled accuracy and efficiency in detecting a wide range of genetic variations. Leveraging state-of-the-art gene sequencing technology, we identify mutations, deletions, insertions, and recombination variations within the GBA gene. For further information regarding the products and services provided, project-specific consultation, and pricing, please submit an inquiry here.

Introduction

Mutations in the GBA (glucocerebrosidase) gene represent a significant genetic risk factor for neurodegenerative diseases, notably Parkinson's Disease (PD) and Gaucher Disease (GD). These mutations disrupt lysosomal function, triggering a cascade of events that contribute to disease progression. Approximately 130 distinct GBA mutations have been identified in PD patients, with the L444P (c. 1448 T>C) and N370S (c. 1226A>G) variants being the most prevalent, accounting for roughly 75% of PD-associated GBA mutations. Individuals carrying GBA mutations often exhibit elevated levels of phosphorylated tau and specific lipids in their plasma. The primary pathological consequence of GBA mutations is the reduced activity or complete loss of function of the encoded GCase enzyme. This deficiency leads to the accumulation of its substrate, glucocerebroside (GLCCER). Excessive GLCCER disrupts protein trafficking, impairs the autophagic-lysosomal pathway, and ultimately interferes with the degradation of α-synuclein. This interference results in α-synuclein aggregation and misfolding, culminating in neuronal dysfunction and contributing to the development of neurodegenerative conditions.

Fig.1 Mechanisms linking GCase, alpha-synuclein and PD.^{1, 3}

Our Technical Benefits

• High-Precision Mutation Detection Technology

The use of advanced high-throughput sequencing technology (such as exome sequencing CES) can efficiently detect point mutations, deletions, insertions, and recombination of GBA genes. Combined with bioinformatics tools and professional teams, in-depth analysis of sequencing data can be performed to provide detailed interpretation of mutations.

Functional validation was supported by a quantitative assessment of the effect of mutations on glucocerebrosidase (GCase) activity. This assessment utilized a luciferase activity assay, which employs a 4-methylumbelliferyl-β-D-glucoside substrate, among others.

• Integrated Multi-Omics Analytics

Provide protein level verification (Western blot, immunohistochemistry) to detect GBA protein expression and localization, e.g. using anti-GBA C-terminal antibodies to detect endoplasmic reticulum transport defects. Combined with multiplex detection of lysosomal enzyme activity (GCase, GLA, GALC, etc.) for high throughput screening.

Case Study: Gcase mRNA and enzyme activity detection in fibroblasts

Fig.2 In fibroblasts from Parkinson's patients with heterozygous GBA mutations, GCase expression and activity were decreased.^{2, 3}

Our GBA mutation assay service utilizes state-of-the-art technology to accurately identify point mutations, deletions/insertions, and gene-pseudogene recombination. This service provides a reliable basis for drug target validation, disease model construction, and clinical trial patient screening. Please contact us now to obtain exclusive solutions, personalized quotes, and technical documents.

References

1. Smith, Laura, and Anthony HV Schapira. "GBA variants and Parkinson disease: mechanisms and treatments." Cells 11.8 (2022): 1261.
2. Sanchez-Martinez, Alvaro, et al. "Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models." Scientific reports 6.1 (2016): 31380.
3. Distributed under Open Access license CC BY 4.0, without modification.