Discovery of Novel Variants on the CHD7 Gene: A Case Series of CHARGE Syndrome

Xiangtao Wu; Liang Chen; Weihong Lu; Shaoru He; Xiaowen Li; Lingling Sun; Longjiang Zhang; Dejuan Wang; Ruigui Zhang; Yumei Liu; Yunxia Sun; Zhichun Feng; Victor Wei Zhang

doi:10.3389/fgene.2022.852429

Discovery of Novel Variants on the CHD7 Gene: A Case Series of CHARGE Syndrome

Front Genet. 2022 Jul 22:13:852429. doi: 10.3389/fgene.2022.852429. eCollection 2022.

Authors

Xiangtao Wu^{1

2

3}, Liang Chen², Weihong Lu³, Shaoru He^{1

2}, Xiaowen Li⁴, Lingling Sun⁵, Longjiang Zhang⁵, Dejuan Wang⁶, Ruigui Zhang², Yumei Liu², Yunxia Sun², Zhichun Feng⁷, Victor Wei Zhang⁸

Affiliations

¹ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
² Department of Neonatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
³ Department of Pediatrics of First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
⁴ Neonatal Diagnosis and Treatment Center, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.
⁵ Shenzhen Children's Hospital, Shenzhen, China.
⁶ Department of Urology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
⁷ Department of Neonatology, Faculty of Pediatrics, Chinese PLA General Hospital, BaYi Children's Hospital, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China.
⁸ AmCare Genomics Lab, Guangzhou, China.

Abstract

Background: CHARGE syndrome (CS) is a single-gene genetic disorder with multiple organ malformations caused by a variant of the chromodomain helicase DNA-binding protein 7 (CHD7) gene on chromosome 8q12.1. In this study, we aimed to investigate new variants that have emerged in these cases compared with typical CS and the relationship between the genes and phenotypes. Methods: Patients with suspected genetic diseases were subjected to Whole Exome Sequencing (WES) at a genetics laboratory in Guangzhou. The average sequencing coverage depth was >200 ×, and 96% was >20 ×. The variant interpretation was manipulated according to the American College of Medical Genetics (ACMG) guidelines. Molecular data on databases for ClinVar and CHD7 were also collected and collated. We reviewed the currently described CHD7 variants and analyzed the genetic variation and phenotypic heterogeneity. Results: Data of 12 patients with CS from four hospitals in China were collected. According to gestational age, most of them (8/12) were near-term babies with a lower birth weight than their peers, averaging 2.62 kg. In this study, the most common phenotypes were respiratory tract malformations (11/12), heart malformations (10/12), and central nervous system malformations (9/12). Two fetuses were confirmed to have brain or heart abnormalities during prenatal testing, while 10/12 were found to have abnormalities during prenatal testing. The maximum Acute Physiology and Chronic Health Evaluation (APACHE II) score at admission was 19, and the average was 11.58. Five variants in the CHD7 gene c.7012C > T (p.Q2338*), c.7868delC (p.P2623Rfs*16), c.5405-3C > G, c.6936 + 2T > C, and c.8077-2A > G) were novel and were located in exons 33, 36, and introns 25, 32, and 37, respectively. There may be a positive correlation between exon location and phenotype. Conclusion: Five novel variants were discovered. These expanded the mutational spectrum of the CHD7 gene and the phenotype of CS. There may be a correlation between the new mutation sites and the phenotype, which has some reference value for the evaluation of mutation sites.

Keywords: CHARGE syndrome; infants; mutation; phenotypes; respiratory malformations.