Table_5_ABCA4 Gene Screening in a Chinese Cohort With Stargardt Disease: Identification of 37 Novel Variants.xls

Purpose: To clarify the mutation spectrum and frequency of ABCA4 in a Chinese cohort with Stargardt disease (STGD1).
Methods: A total of 153 subjects, comprising 25 families (25 probands and their family members) and 71 sporadic cases, were recruited for the analysis of ABCA4 variants. All probands with STGD1 underwent a comprehensive ophthalmologic examination. Overall, 792 genes involved in common inherited eye diseases were screened for variants by panel-based next-generation sequencing (NGS). Variants were filtered and analyzed to evaluate possible pathogenicity.
Results: The total variant detection rate of at least one ABCA4 mutant allele was 84.3% (129/153): two or three disease-associated variants in 86 subjects (56.2%), one mutant allele in 43 subjects (28.1%), and no variants in 24 subjects (15.7%). Ninety-six variants were identified in the total cohort, which included 62 missense (64%), 15 splicing (16%), 11 frameshift (12%), 6 nonsense (6%), and 2 small insertion or deletion (2%) variants. Thirty-seven novel variants were found, including a de novo variant, c.4561delA. The most prevalent variant was c.101_106delCTTTAT (10.5%), followed by c.2894A > G (6.5%) and c.6563T > C (4.6%), in STGD1 patients from eastern China.
Conclusion: Thirty-seven novel variants were detected using panel-based NGS, including one de novo variant, further extending the mutation spectrum of ABCA4. The common variants in a population from eastern China with STGD1 were also identified.

研究目的：明确中国斯塔加特病（Stargardt disease, STGD1）队列中ABCA4基因的突变谱与突变频率。
研究方法：本研究共纳入153名受试者，涵盖25个家系（含25名先证者及其家庭成员）与71例散发病例，用于ABCA4基因变异的分析。所有确诊STGD1的先证者均接受了全面的眼科检查。研究采用基于靶向测序组的下一代测序（panel-based next-generation sequencing, NGS）技术，对792种常见遗传性眼病相关基因进行变异筛查；随后对筛选得到的变异进行过滤与分析，以评估其潜在致病性。
研究结果：至少携带1个ABCA4突变等位基因的总变异检出率为84.3%（129/153）：其中86名受试者携带2或3个疾病相关变异（占比56.2%），43名受试者仅携带1个突变等位基因（占比28.1%），24名受试者未检出任何变异（占比15.7%）。本队列中共鉴定出96种变异，包括62种错义变异（64%）、15种剪接位点变异（16%）、11种移码变异（12%）、6种无义变异（6%）以及2种小型插入缺失变异（2%）。此外发现37种新发变异，其中包含1个新生变异c.4561delA。在中国东部地区的STGD1患者中，最常见的变异为c.101_106delCTTTAT（占比10.5%），其次为c.2894A>G（占比6.5%）与c.6563T>C（占比4.6%）。
研究结论：本研究通过基于靶向测序组的下一代测序技术共检测出37种新发变异（含1个新生变异），进一步拓展了ABCA4基因的突变谱；同时明确了中国东部地区STGD1人群的常见变异类型。