Department of Ophthalmology & Visual Sciences, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada.
Department of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada.
Eur J Hum Genet. 2021 Aug;29(8):1171-1185. doi: 10.1038/s41431-021-00872-3. Epub 2021 Mar 29.
Inherited retinal dystrophies (IRDs) affect 1 in 3000 individuals worldwide and are genetically heterogeneous, with over 270 identified genes and loci; however, there are still many identified disorders with no current genetic etiology. Whole exome sequencing (WES) provides a hypothesis-free first examination of IRD patients in either a clinical or research setting to identify the genetic cause of disease. We present a study of IRD in ten families from Alberta, Canada, through the lens of novel gene discovery. We identify the genetic etiology of IRDs in three of the families to be variants in known disease-associated genes, previously missed by clinical investigations. In addition, we identify two potentially novel associations: LRP1 in early-onset drusen formation and UBE2U in a multi-system condition presenting with retinoschisis, cataracts, learning disabilities, and developmental delay. We also describe interesting results in our unsolved cases to provide further information to other investigators of these blinding conditions.
遗传性视网膜疾病（IRDs）在全球范围内影响每 3000 人中的 1 人，具有遗传异质性，超过 270 个已确定的基因和基因座；然而，仍有许多已确定的疾病没有当前的遗传病因。全外显子组测序（WES）为临床或研究环境中的 IRD 患者提供了一种无假设的初步检查，以确定疾病的遗传原因。我们通过新基因发现的视角，研究了来自加拿大阿尔伯塔省的十个 IRD 家族。我们确定了其中三个家族的 IRD 的遗传病因是已知疾病相关基因中的变异，这些变异先前被临床研究所忽略。此外，我们还发现了两个潜在的新关联：LRP1 与早发性玻璃膜疣形成有关，UBE2U 与一种多系统疾病有关，该疾病表现为视网膜劈裂、白内障、学习障碍和发育迟缓。我们还描述了未解决病例中的有趣结果，为这些致盲疾病的其他研究者提供了进一步的信息。
