Clinical phenotype and molecular genetic analysis of seven children with CHARGE syndrome
10.3760/cma.j.cn511374-20230723-00012
- VernacularTitle:CHARGE综合征7例患儿的临床表型及分子遗传学分析
- Author:
Lili GE
1
;
Jinghui KONG
;
Chongfen CHEN
;
Zhiyi XIA
;
Shiyue MEI
;
Yaodong ZHANG
Author Information
1. 郑州大学附属儿童医院，河南省儿童医院郑州儿童医院，河南省儿童遗传代谢性疾病重点实验室，郑州 450018
- Keywords:
CHARGE syndrome;
CHD7 gene;
Multiple congenital malformations
- From:
Chinese Journal of Medical Genetics
2024;41(9):1053-1058
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical phenotype and genetic etiology for seven children with CHARGE syndrome (CS).Methods:Clinical data of 7 children with CS diagnosed between March 2020 and December 2022 at the Children′s Hospital Affiliated to Zhengzhou University were analyzed. Genomic DNA was extracted from peripheral blood samples from the children and their parents, and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliatedto Zhengzhou University (Ethics No. 2024-K-023).Results:The ages of the children had ranged from 1 day after birth to 12 years old, and all of them had shown growth retardation. The reasons for their admission had included postnatal breathing, swallowing and feeding difficulties in five cases. One child was found to have abnormal external genitalia in conjunct with hearing impairment, whilst another child had shown no secondary sexual characteristics during puberty. All of the children were found to harbor CHD7 gene variants, which included 3 nonsense variants, 2 frameshifting variants and 2 missense variants, i. e., c. 6292C>T (p.R2098*), c.2754G>A (p.W918*), c. 469C>T (p.R157*), c. 3308T>A (p.V1103D), c. 7111delC (p.Q2371Kfs), c. 6023delA (p.D2008Vfs) and c. 3565C>T (p.R1189C). All of the variants were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 3308T>A (p.V1103D) and c. 3565C>T (p.R1189C) variants were rated as likely pathogenic (PS2+ PM2_Supporting+ PP3), whilst the remainders were rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:There is strong clinical and genetic heterogeneity in CS. Early genetic testing may facilitate accurate diagnosis. The detection of novel variants has expanded the phenotypic spectrum of CS and the mutational spectrum of the CHD7 gene.
