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Abstract：
Background: Inherited ocular conditions are a frequent cause of blindness. Gene therapy has encouraged the development of genetic testing, currently able to detect up to 80% of mutations in contrast to the 5% sensitivity achieved a few decades ago.Materials and methods: One hundred sixty-three patients with suspected genetic ocular disorders who were referred to a single clinician between August 2014 and August 2019 underwent a thorough ophthalmologic examination. Those diagnosed with congenital cataract, retinoblastoma, anterior segment dysgenesis, autoimmune retinal disease, posterior microphthalmia, or cobalamin C deficiency were excluded, along with patients who opted against genetic testing. Included probands were classified into a diagnostic clinical category and offered genetic testing. Blood samples were sent to foreign accredited diagnostic laboratories, followed by clinical interpretation of the results.Results: Of the 163 patients referred, 104 were enrolled in the study. Median age at disease onset was 2 years (range, 0 to 43 years). A molecular diagnosis was established at a median age of 10 years (range, 0.4 to 50 years). Disease-causing genotypes were identified in 82 of the probands, indicating a mutation detection rate of 78.8%. Mutations were identified in 38 genes, ABCA4 being the most commonly affected (23% of mutations), followed by CRB1 (13% of mutations). Whole-exome sequencing was performed in 6 patients, resulting in a definite diagnosis in 3 (50%).Conclusions: Molecular testing for inherited ocular conditions is feasible in developing countries by sending samples to certified foreign laboratories, with a mutation detection rate comparable to published values in developed countries. Further studies to identify more disease-causing genes may improve the overall sensitivity.
摘要：
背景：遗传性眼部疾病是导致失明的常见原因。基因疗法促进了基因检测的发展，目前能够检测到高达80％的突变，而几十年前达到5％的灵敏度。材料和方法：2014年8月至2019年8月期间，有163例疑似遗传性眼部疾病患者转诊给一名临床医生，接受了彻底的眼科检查。那些被诊断患有先天性白内障的人，视网膜母细胞瘤,眼前节发育不全，自身免疫性视网膜疾病，后部小眼症，或钴胺C缺乏症被排除，以及选择不进行基因检测的患者.纳入的先证者被归类为诊断临床类别，并提供基因检测。血液样本被送到外国认可的诊断实验室，随后对结果进行临床解释。结果：在转诊的163例患者中，104人参加了这项研究。发病时的中位年龄为2岁(范围，0至43年）。分子诊断的中位年龄为10岁(范围，0.4至50年）。在82名先证者中发现了致病基因型，表明突变检出率为78.8%。在38个基因中发现了突变，ABCA4是最常见的影响（23％的突变），其次是CRB1（13％的突变）。对6例患者进行了全外显子组测序，导致3（50％）的明确诊断。结论：通过将样本发送到经过认证的外国实验室，在发展中国家对遗传性眼部疾病进行分子检测是可行的，突变检出率与发达国家公布的值相当。进一步的研究，以确定更多的致病基因可能会提高整体的敏感性。
