Clinical and Genetic Analysis of CHD7 Expands the Genotype and Phenotype of CHARGE Syndrome.

Zailong Qin,Jingsi Luo,Sheng Yi,Wei Li,Weiliang Lu,Fei Chen,Limei Huang,Shang Yi,Mengting Li,Qi Yang,Haiyang Zheng,Jing Xu,Yiping Shen,Qiang Zhang,Jiasun Su

doi:10.3389/fgene.2020.00592

Zailong Qin, Jingsi Luo + Show 13 more

Open Access

https://doi.org/10.3389/fgene.2020.00592

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Abstract

CHARGE syndrome is a life-threatening disease caused by mutations of chromodomain helicase DNA-binding protein 7 gene (CHD7). The disease is characterized by a pattern of congenital anomalies that involve multiple organs. In this study, five patients were diagnosed as CHARGE syndrome with CHD7 mutations by whole exome sequencing. Although the clinical phenotypes of probands are highly variable and typical symptoms such as coloboma and choanal atresia are not commonly manifested in this cohort, they all presented congenital heart defects. Of note, dyspnea is the most prominent symptom in all five neonatal patients, suggesting that dyspnea might be a phenotypic clue of CHARGE syndrome.

Highlights

CHARGE syndrome (OMIM#214800), a rare congenital disorder, occurs in approximately 1/8,5000 to 1/15,000 livebirths
Genotype analysis of chromodomain helicase DNA-binding protein 7 (CHD7) based on ClinVar and CHD7 database demonstrated the mutation spectrum and phenotypes of CHARGE syndrome which might be contributed to the study of CHD7 mutation-associated CHARGE syndrome
CHARGE syndrome is a genetic disorder with highly variable phenotypes even within a family and results from mutations of CHD7 gene

Summary

INTRODUCTION

CHARGE syndrome (OMIM#214800), a rare congenital disorder, occurs in approximately 1/8,5000 to 1/15,000 livebirths It previously described by Hall and Hittner et al as association of coloboma, choanal atresia, and congenital heart defects and summarized by Pagon et al as the acronym of multiple anomalies, including Coloboma of eye, Heart defects, Atresia of choanae, Retardation of growth and/or development, Genitourinary defects and/or hypogonadism, and Ear anomalies with or without deafness (Hall, 1979; Hittner et al, 1979). Genotype analysis of CHD7 based on ClinVar and CHD7 database demonstrated the mutation spectrum and phenotypes of CHARGE syndrome which might be contributed to the study of CHD7 mutation-associated CHARGE syndrome Both reported phenotypes and the mutation spectrum in this study can facilitate the development of prenatal screening for CHARGE syndrome. Our findings may provide new molecular evidence and expand the phenotypes for CHARGE syndrome which would be helpful for clinical diagnosis

MATERIALS AND METHODS

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