Nair Pratibha, Sabbagh Sandra, Mansour Hicham, Fawaz Ali, Hmaimess Ghassan, Noun Peter, Dagher Rawane, Megarbane Hala, Hana Sayeeda, Alame Saada, Lamaa Maher, Hasbini Dana, Farah Roula, Rajab Mariam, Stora Samantha, El-Tourjuman Oulfat, Abou Jaoude Pauline, Chalouhi Gihad, Sayad Rony, Gillart Anne-Celine, Al-Ali Mahmoud, Delague Valerie, El-Hayek Stephany, Mégarbané André
Centre for Arab Genomic Studies, Dubai, UAE.
Pediatric Department, Hôtel Dieu de France Hospital, Beirut, Lebanon.
Mol Genet Genomic Med. 2018 Nov;6(6):1041-1052. doi: 10.1002/mgg3.480. Epub 2018 Oct 7.
According to the Catalogue of Transmission Genetics in Arabs, less than half of diseases reported in Lebanese patients are mapped. In the recent years, Next Generation Sequencing (NGS) techniques have significantly improved clinical diagnosis, compared to traditional sequencing methods.
A total of 213 analyses by NGS (167 by whole exome sequencing (WES) and 46 by multigene panels tests) were performed on pediatric patients across different regions of Lebanon over a period of two years (December 2015-December 2017).
Neurological disorders were the most frequent referral demand for both WES and gene panels (122/213). Pathogenic, likely pathogenic, or variants of unknown significance were identified in 69.5% of the WES and panel patients combined. Over half of the patients with such variants had an autosomal recessive disorder. A definite molecular diagnosis (pathogenic or likely pathogenic variants) was achieved in 34.1% and 47.8% of the patients studied by WES and the multigene panels, respectively. Thirty-three novel variants were found in the cases that were molecularly solved; 26 of these being identified by WES and seven by the multigene panels. In three consanguineous families, autosomal recessive inheritance of genes previously reported as showing dominant inheritance patterns were found. Biallelism was found in six cases, digenism in four cases, and one case was trigenic.
Our study thus suggests that NGS tools are valuable for an improved clinical diagnosis, and highlights that the increased adoption of such techniques will significantly further improve our understanding of the genetic basis of inherited diseases in Lebanon.
根据《阿拉伯人遗传传递目录》，黎巴嫩患者报告的疾病中不到一半已被定位。近年来，与传统测序方法相比，新一代测序（NGS）技术显著改善了临床诊断。
在两年时间（2015年12月至2017年12月）内，对黎巴嫩不同地区的儿科患者进行了总共213次NGS分析（167次全外显子测序（WES）和46次多基因panel检测）。
神经系统疾病是WES和基因panel最常见的转诊需求（122/213）。在WES和panel患者合并组中，69.5%的患者鉴定出了致病、可能致病或意义未明的变异。超过一半有此类变异的患者患有常染色体隐性疾病。通过WES和多基因panel研究的患者中，分别有34.1%和47.8%获得了明确的分子诊断（致病或可能致病变异）。在分子诊断明确的病例中发现了33个新变异；其中26个由WES鉴定，7个由多基因panel鉴定。在三个近亲家庭中，发现先前报道显示显性遗传模式的基因呈常染色体隐性遗传。发现双等位基因的有6例，双基因的有4例，三基因的有1例。
因此，我们的研究表明NGS工具对改善临床诊断很有价值，并强调增加此类技术的应用将显著进一步提高我们对黎巴嫩遗传性疾病遗传基础的理解。
