AI Article Synopsis
- This study focuses on autosomal recessive bestrophinopathy (ARB), a retinal disease linked to mutations in the BEST1 gene, leading to visual loss and retinal degeneration in affected individuals.
- Researchers used advanced sequencing techniques, specifically Pacific Biosciences' SMRT sequencing and Sanger sequencing, to identify two new mutations in the BEST1 gene from two Chinese families with ARB.
- The findings demonstrate the effectiveness of third-generation sequencing for detecting genetic mutations, expanding the knowledge of BEST1 mutations in the Chinese population and emphasizing its potential for future genetic studies.
Article Abstract
Objective: Autosomal recessive bestrophinopathy (ARB), a retinal degenerative disease, is characterized by central visual loss, yellowish multifocal diffuse subretinal deposits, and a dramatic decrease in the light peak on electrooculogram. The potential pathogenic mechanism involves mutations in the BEST1 gene, which encodes Ca-activated Cl channels in the retinal pigment epithelium (RPE), resulting in degeneration of RPE and photoreceptor. In this study, the complete clinical characteristics of two Chinese ARB families were summarized.
Methods: Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing was performed on the probands to screen for disease-causing gene mutations, and Sanger sequencing was applied to validate variants in the patients and their family members.
Results: Two novel mutations, c.202T>C (chr11:61722628, p.Y68H) and c.867+97G>A, in the BEST1 gene were identified in the two Chinese ARB families. The novel missense mutation BEST1 c.202T>C (p.Y68H) resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1. Another novel variant, BEST1 c.867+97G>A (chr11:61725867), located in intron 7, might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.
Conclusion: Our findings represent the first use of third-generation sequencing (TGS) to identify novel BEST1 mutations in patients with ARB, indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes. The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.
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| http://dx.doi.org/10.1007/s11596-024-2865-3 | DOI Listing |
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