Abstract
Objective
CHARGE syndrome is a rare autosomal dominant (AD) multi-system disorder with a broad and variable clinical manifestation and occurs in approximately 1/10,000 newborns in the world. Mutations in the CHD7 gene are the genetic cause of over 90% of patients with typical CHARGE syndrome. The present study reported a novel variant in the CHD7 gene in a Chinese family with an abnormal fetus.
Methods
Routine prenatal ultrasound screening showed fetal heart abnormality and left foot varus. Chromosomal microarray analysis (CMA) and fetus-parent whole-exome sequencing (trio-WES) were performed to determine the genetic cause of the fetus. The candidate variant was further verified using Sanger sequencing.
Results
CMA analysis revealed normal results. However, WES analysis identified a de novo heterozygous variant of c.2919_2922del (NM_017780.4) on exon 11 of CHD7 gene, resulting in a premature truncation of the CHD7 protein (p.Gly975*). The variant was classified as Pathogenic (PVS1 + PS2_Moderate + PM2_Supporting) based on the ACMG guidelines. Combined with the clinical phenotype of fetal heart abnormalities, it was confirmed CHARGE syndrome.
Conclusion
We identified a novel heterozygous variant c.2919_2922del in CHD7 of a Chinese fetus with CHARGE syndrome, enriching the genotype-phenotype spectrum of CHD7. These results suggest that genetic testing could help facilitate prenatal diagnosis of CHARGE syndrome, thus promoting the appropriate genetic counseling.
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Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
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YS and LY performed most of WES analysis and prepared the manuscript. LL, XG and JJ analyzed, interpreted the data, and modified the manuscript. All authors discussed the data and read the manuscript.
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Yanhong Shan, LingFang Yao, Linli Li, Xueping Gao, Jinghan Jiang declare that they have no conflict of interest.
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This study had been approved by the Huangshi love &health hospital affiliated of Hubei Polytechnic University. Informed consent was obtained from all individual participants included in the study.
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Shan, Y., Yao, L., Li, L. et al. A novel CHD7 variant in a chinese family with CHARGE syndrome. Genes Genom 46, 379–387 (2024). https://doi.org/10.1007/s13258-023-01411-8
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DOI: https://doi.org/10.1007/s13258-023-01411-8