Tao Zhiyan, Lu Fang
Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 640000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Jan 10;38(1):42-46. doi: 10.3760/cma.j.cn511374-20200622-00461.
To explore the genetic basis for three children patients with CHARGE syndrome.
The three children and their parents were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.
All patients had ocular anomalies including microphthalmia, microcornea, lens opacity, and coloboma of iris, optic nerve, retina and choroid. And all were found to carry heterozygous variants of the CHD7 gene, which included two frameshifting variant, namely c.1447delG (p.Val483Leufs12) and c.1021_1048delAATCAGTCCGTACCAAGATACCCCAATG (p.Asn341Leufs2) in exon 2, which were unreported previously and were pathogenic based on the American College of Medical Genetics and Genomics standards and guidelines (PVS1+PM2+PM6), and a nonsense variant c.7957C>T (p.Arg2653*) in exon 36, which was known to be likely pathogenic (PVS1+PM2+PP4). Sanger sequencing confirmed that the two frameshifting mutations were de novo, and the nonsense mutation was also suspected to be de novo.
Pathological variants of the CHD7 gene probably underlay the CHARGE syndrome in the three patients.
探究3例CHARGE综合征患儿的遗传基础。
对3例患儿及其父母进行全外显子组测序，并通过桑格测序验证候选变异。
所有患者均有眼部异常，包括小眼症、小角膜、晶状体混浊以及虹膜、视神经、视网膜和脉络膜缺损。所有患者均被发现携带CHD7基因的杂合变异，其中包括2个移码变异，即外显子2中的c.1447delG（p.Val483Leufs12）和c.1021_1048delAATCAGTCCGTACCAAGATACCCCAATG（p.Asn341Leufs2），这两个变异此前未被报道，根据美国医学遗传学与基因组学学会的标准和指南判定为致病（PVS1+PM2+PM6）；以及外显子36中的无义变异c.7957C>T（p.Arg2653*），已知该变异可能致病（PVS1+PM2+PP4）。桑格测序证实，这两个移码突变是新生突变，该无义突变也疑似为新生突变。
CHD7基因的病理性变异可能是这3例患者患CHARGE综合征的病因。
