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In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Exome capture sequencing identifies a novel mutation in BBS4.
Hui Wang1, Xianfeng Chen, Lynn Dudinsky
1Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Molecular Vision
|January 6, 2012
Summary
Researchers identified a new mutation in the BBS4 gene causing Leber congenital amaurosis (LCA), a severe inherited retinal disease. This finding advances understanding of BBS4 function in the retina.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Leber congenital amaurosis (LCA) is a severe inherited retinal dystrophy causing early-onset vision loss.
- LCA accounts for approximately 5% of all retinal dystrophies.
Purpose of the Study:
- Identify a novel LCA disease allele or gene.
- Combine genetic mapping with whole exome sequencing to find LCA-causing mutations.
Main Methods:
- Whole genome SNP genotyping and whole exome sequencing were performed on patients.
- Sanger sequencing validated the identified mutation.
- Zebrafish models were used for functional analysis of the mutant allele.
Main Results:
- A novel missense mutation (c.253G>C;p.E85Q) in the Bardet-Biedl syndrome 4 protein (BBS4) gene was identified in a Saudi Arabian family.
- The mutation segregated with LCA and was absent in population databases and controls.
- Zebrafish studies confirmed the pathogenicity of the G253C allele, showing it impairs rhodopsin localization.
Conclusions:
- The identified BBS4 mutation likely reduces or abolishes BBS4 function in the retina.
- Further research on this allele will illuminate the complex functions of BBS4.
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