Maternal CHD7 gonosomal mosaicism in a fetus with CHARGE syndrome.

Ting Bai, Ying Shen, Yanting Yang, Siyu Dai, Hongqian Liu

American journal of medical genetics. Part A 2024 Apr

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Parental mosaicism is important in families with de novo mutations. Herein, we report a case of fetal CHARGE syndrome (CS) with a CHD7 variant inherited from maternal CHD7 gonosomal mosaicism. The variant was detected through trio-based whole-exome sequencing and Sanger sequencing. High-depth whole-exome sequencing was performed for the identification of parental mosaicism. A novel heterozygous CHD7 nonsense mutation (c.5794G>T/ p.E1932*) was detected in the tissue from the aborted fetus. The parents were wild-type, indicating that the mutation was a de novo variant. The mutation was suspected to be the cause of the fetal CS. However, high-depth whole-exome sequencing revealed maternal gonosomal mosaicism at a variant allele frequency of 3.2%-23.3%. The variant was identified in various tissues (peripheral blood, hair follicles, buccal epithelia, and pharyngeal epithelia) from the asymptomatic mother. We confirmed maternal CHD7 gonosomal mosaicism as a genetic cause of fetal CS. Our results emphasize the importance of clinical analysis in accurately determining the parents' status in detecting the CHD7 de novo variant in fetal CS, as this analysis has vital implications for evaluating the recurrence risk for genetic counseling. © 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.

Citation

Ting Bai, Ying Shen, Yanting Yang, Siyu Dai, Hongqian Liu. Maternal CHD7 gonosomal mosaicism in a fetus with CHARGE syndrome. American journal of medical genetics. Part A. 2024 Apr;194(4):e63491