Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, 110060, India.
Indian J Pediatr. 2018 Mar;85(3):228-236. doi: 10.1007/s12098-017-2453-7. Epub 2017 Oct 2.
The authors review the utility of genetic testing in ophthalmic disorders - precise diagnosis, accurate prognosis, genetic counseling, prenatal diagnosis, and entry into gene-specific therapeutic trials. The prerequisites for a successful outcome of a genetic test are an accurate clinical diagnosis, a careful family history that guides which genes to study, and genetic counseling (both pre-test and post-test). The common eye disorders for which genetic testing is commonly requested are briefly discussed - anophthalmia, microphthalmia, coloboma, anterior segment dysgenesis, corneal dystrophies, cataracts, optic atrophy, congenital glaucoma, congenital amaurosis, retinitis pigmentosa, color blindness, juvenile retinoshisis, retinoblastoma etc. A protocol for genetic testing is presented. If specific mutations in a gene are common, they should form the first tier test, as the mutations in Leber hereditary optic neuropathy. If mutations in one gene are likely, sequencing of that gene should be carried out, e.g. GALT gene in galactosemia, RS1 gene in retinoshisis. Disorders with genetic heterogeneity require multi-gene panel tests, and if these show no abnormality, then deletion / duplication or microarray studies are recommended, followed in sequence by clinical exome (5000 to 6000 genes), full exome (about 20,000 genes or whole genome studies (includes all introns). It is fortunate that most genetic tests in ophthalmology are available in India, including gene panel and whole exome/genome sequencing tests.
作者回顾了遗传测试在眼科疾病中的应用 - 精确诊断、准确预后、遗传咨询、产前诊断和进入基因特异性治疗试验。遗传测试成功的前提是准确的临床诊断、指导研究哪些基因的详细家族史,以及遗传咨询(包括测试前和测试后)。简要讨论了常见的请求进行遗传测试的眼科疾病 - 无眼症、小眼症、裂眼病、前节发育不良、角膜营养不良、白内障、视神经萎缩、先天性青光眼、先天性黑蒙、视网膜色素变性、色盲、青少年性视网膜劈裂症、视网膜母细胞瘤等。提出了遗传测试方案。如果特定基因的突变很常见,它们应该作为第一个层次的测试,如莱伯遗传性视神经病变的突变。如果一个基因的突变很可能,则应进行该基因的测序,例如半乳糖血症中的 GALT 基因、视网膜劈裂症中的 RS1 基因。具有遗传异质性的疾病需要进行多基因面板测试,如果这些测试没有异常,则建议进行缺失/重复或微阵列研究,然后按顺序进行临床外显子组(5000 至 6000 个基因)、全外显子组(约 20,000 个基因)或全基因组研究(包括所有内含子)。幸运的是,印度提供了大多数眼科遗传测试,包括基因面板和全外显子/基因组测序测试。