Next generation sequencing-based molecular diagnosis in familial congenital cataract expands the mutational spectrum in known congenital cataract genes
Next generation sequencing-based molecular diagnosis in familial congenital cataract expands the mutational spectrum in known congenital cataract genes
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DOI：
10.1002/ajmg.a.40524
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发表时间：
2018-12-01
影响因子：
2
通讯作者：
Zenteno, Juan C.
中科院分区：
文献类型：
--
作者：
Astiazaran, Mirena C.;Garcia-Montano, Leopoldo A.;Zenteno, Juan C.
先天性白内障（Congenital Cataract，CC）是世界范围内儿童致盲的重要原因。CC是一种遗传异质性疾病，因为超过40个基因的突变已被证明会导致疾病，高达40%的病例来自单基因突变。因此，下一代脱氧核糖核酸测序（NGS）是一个合适的方法CC分子诊断。在这项研究中，我们使用商业上可获得的遗传性疾病NGS面板，包括50个CC基因的遗传诊断11例先证者与遗传性CC。在6个家庭中确认了因果变异。A novel p53 GC variant，p.（Phe 6Ser），在两个明显无关的家庭中被确定。晶体蛋白基因中的另外两种新变体RMBB 2（p. [Gly 149 Asp]）和GlyGA（p. [Arg48Cys]）。一个家庭携带了这本小说。[Gly8_Leu11del]变异，而另一个家族表现出先前报道的EPHA 2中的c.2826- 9 G>A致病性变化。我们的研究结果说明了NGS在我们人群中诊断CC的实用性，我们的研究结果有助于扩大已知CC基因中四种新型致病性变体的突变谱。
Congenital cataract (CC) is a significant cause of childhood blindness worldwide. CC is a genetically heterogeneous disease because mutations in over 40 genes have been demonstrated to cause the disorder and up to 40% of cases arise from single-gene mutations. Hence, next generation sequencing (NGS) of deoxyribonucleic acid is a suitable approach for CC molecular diagnosis. In this study, we used commercially available inherited disease NGS panels including 50 CC genes for the genetic diagnosis of 11 probands with hereditary CC. Causal variants were recognized in six families. A novel CRYGC variant, p.(Phe6Ser), was identified in two apparently unrelated families. Two additional novel variants in the crystallin genes CRYBB2 (p.[Gly149Asp]) and CRYGA (p.[Arg48Cys]) were also identified. One family carried the novel p.[Gly8_Leu11del] variant in GJA8, while another family exhibited the previously reported c.2826-9G>A pathogenic change in EPHA2. Our results illustrate the utility of NGS for diagnosing CC in our population, and our results contribute to expand the mutational spectrum with four novel pathogenic variants in known CC genes.