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Published on: November 5, 2019
Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks
Naoyuki Sato1, Tomohiro Nakayama, Yoshihiro Mizutani
1Divisions of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan.
Insights
Researchers identified six causal mutations for angioid streaks (AS), a rare eye condition. Four of these mutations in the ABCC6 gene are novel, advancing understanding of AS and pseudoxanthoma elasticum (PXE).
Area of Science:
- Ophthalmology
- Genetics
- Medical Research
Background:
- Angioid streaks (AS) are characterized by breaks in Bruch's membrane.
- AS is frequently associated with pseudoxanthoma elasticum (PXE).
- The ABCC6 gene is implicated in PXE, but its role in AS is unclear.
Purpose of the Study:
- To identify the causal gene mutations responsible for angioid streaks (AS).
- To investigate the association between the ABCC6 gene and AS.
- To utilize a haplotype-based case-control study for mutation discovery.
Main Methods:
- Genotyping of 54 Japanese AS patients and 150 controls using 5 single-nucleotide polymorphisms (SNPs).
- Performing a simple association study and a haplotype-based case-control study.
- Gene sequencing of AS patients with identified special haplotypes.
Main Results:
- Six causal mutations for AS were identified: p.R419Q, p.E422K, c.2542delG, Del_Exon23, c.3774-3775insC, and p.E1427K.
- Four of the identified mutations are novel.
- The study successfully isolated causative mutations for AS.
Conclusions:
- The ABCC6 gene harbors causal mutations for angioid streaks.
- The haplotype-based approach is effective for identifying disease-causing mutations.
- This methodology can aid in discovering susceptibility variants for complex diseases and mutations in monogenic disorders.
Abstract:
Angioid streaks (AS) are eye abnormalities caused by breaks in Bruch's membrane. The condition is often associated with pseudoxanthoma elasticum (PXE). The ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6) is reported to be the causal gene for PXE, although there have been no reports on whether the ABCC6 gene is the causal gene for AS. The aims of this study are to isolate the causal mutations for AS using a haplotype-based case-control study. We genotyped 54 Japanese AS patients and 150 controls for 5 single-nucleotide polymorphisms (SNPs). A simple association study using each SNP and a haplotype-based case-control study were performed. Twelve patients with special haplotypes for AS were selected, and were then subjected to gene sequencing. Six variants were successfully identified as causal mutations for AS (p.R419Q, p.E422K, c.2542delG, Del_Exon23, c.3774-3775insC and p.E1427K), and 4 of these were novel. This method can be applied to both identifying susceptibility variants of multifactorial diseases and isolating mutations in single-gene diseases.
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