ABCA4 gene screening by next-generation sequencing in a British cohort
Kaoru Fujinami1, Jana Zernant, Ravinder K Chana
1Laboratory of Visual Physiology, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan.
Investigative Ophthalmology & Visual Science
|August 29, 2013
Summary
Next-generation sequencing (NGS) identified novel mutations in the ABCA4 gene for patients with ABCA4-associated disease. This efficient screening method aids in diagnosing genetic eye conditions and developing targeted therapies.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- ABCA4-associated diseases are a group of inherited retinal disorders.
- Previous diagnostic methods, like microarrays, often identify only one disease-causing variant.
Purpose of the Study:
- To apply a next-generation sequencing (NGS) strategy for screening the ABCA4 gene in a British cohort.
- To identify novel mutations in patients with ABCA4-associated disease.
Main Methods:
- 79 patients with a clinical diagnosis and one identified ABCA4 variant were selected.
- The entire coding and adjacent intronic sequences of the ABCA4 gene were sequenced using NGS.
- Variants were confirmed by Sanger sequencing and pathogenicity was assessed using in silico analysis.
Main Results:
- NGS detected 42 variants, with 39 classified as disease-causing.
- 31 of these disease-causing variants were novel, including missense, splice-site, nonsense, and frameshift mutations.
- Disease-causing variants were confirmed in 47% of patients, with one variant in 46%, and none in 7%.
Conclusions:
- NGS effectively identified the second disease-associated ABCA4 allele in about half of the patients.
- This time- and cost-efficient NGS strategy is valuable for screening large cohorts.
- The method will be increasingly important with the development of ABCA4-directed therapies.
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