Original Article
Clinical and genetic analysis of two patients with CHARGE syndrome due to de novo variants of CHD7 gene
Dong Yan, Shi Xiaoyi, Du Kaixian, Shi Yali, Wang Jun, Jia Tianming, Zhang Ke, Xu Ruijuan, Wang Lijun
Published 2022-04-10
Cite as Chin J Med Genet, 2022, 39(4): 387-391. DOI: 10.3760/cma.j.cn511374-20210405-00303
Abstract
ObjectiveTo analyze the clinical characteristics and genetic basis of two children patients with CHARGE syndrome.
MethodsThe 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.
ResultsChild 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.
ConclusionThe special clinical phenotypes shown by the two children harboring novel CHD7 variants have further expanded the phenotypic spectrum of CHARGE syndrome.
Key words:
CHARGE syndrome; Infantile spasm; Cerebellar vermis dysplasia; Widening of fourth ventricle; Congenital hip dysplasia
Contributor Information
Dong Yan
Department of Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Shi Xiaoyi
Department of Pediatric Development and Behavior, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Du Kaixian
Department of Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Shi Yali
Department of Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Wang Jun
Department of Pediatric Rehabilitation, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Jia Tianming
Department of Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Zhang Ke
Department of Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Xu Ruijuan
Department of Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Wang Lijun
Department of Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
