Dong Yan, Shi Xiaoyi, Du Kaixian, Shi Yali, Wang Jun, Jia Tianming, Zhang Ke, Xu Ruijuan, Wang Lijun
Department of Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Apr 10;39(4):387-391. doi: 10.3760/cma.j.cn511374-20210405-00303.
To analyze the clinical characteristics and genetic basis of two children patients with CHARGE syndrome.
The clinical features of the two patients were analyzed, and potential variants were detected by Trio whole exome sequencing (trio-WES) of the probands and their parents.
Child 1 has manifested cerebellar vermis dysplasia, enlargement of cerebral ventricles, whereas child 2 manifested with infantile spasm and congenital hip dysplasia. Both children were found to harbor de novo heterozygous variants of the CHD7 gene, namely c.4015C>T (exon 17) and c.5050G>A (exon 22). Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were rated as pathogenic variants, and the related disease was CHARGE syndrome. Furthermore, child 2 was also found to harbor a novel heterozygous c.6161A>C (p.Gln2054Pro) missense variant of COL12A1 gene, which was rated as possibly pathogenic, and the associated disease was Bethlem myopathy type 2, which is partially matched with the patient' s clinical phenotype.
The special clinical phenotypes shown by the two children harboring novel CHD7 variants have further expanded the phenotypic spectrum of CHARGE syndrome.
分析2例CHARGE综合征患儿的临床特征及遗传基础。
分析2例患者的临床特征，并通过对先证者及其父母进行三联体全外显子测序（trio-WES）检测潜在变异。
患儿1表现为小脑蚓部发育不全、脑室扩大，而患儿2表现为婴儿痉挛症和先天性髋关节发育不良。2例患儿均发现CHD7基因的新生杂合变异，即c.4015C>T（外显子17）和c.5050G>A（外显子22）。根据美国医学遗传学与基因组学学会的指南，这两个变异被评为致病变异，相关疾病为CHARGE综合征。此外，患儿2还发现COL12A1基因存在一个新的杂合c.6161A>C（p.Gln2054Pro）错义变异，被评为可能致病，相关疾病为2型贝斯勒肌病，与患者的临床表型部分相符。
这2例携带新CHD7变异的患儿所表现出的特殊临床表型进一步扩展了CHARGE综合征的表型谱。
