Abstract：
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.
摘要：
父母镶嵌在具有从头突变的家庭中很重要。在这里，我们报告了一例胎儿CHARGE综合征（CS），其CHD7变异体遗传自母体CHD7性腺嵌合体。通过基于三重的全外显子组测序和Sanger测序检测变体。进行高深度全外显子组测序以鉴定亲本镶嵌性。在来自流产胎儿的组织中检测到新的杂合CHD7无义突变(c.579G>T/p.E1932*)。父母是野生型,表明突变是从头变异。该突变被怀疑是胎儿CS的原因。然而,高深度全外显子组测序显示，在3.2%-23.3%的变异等位基因频率下，母体的性腺体镶嵌性。在各种组织（外周血，毛囊,颊上皮,和咽上皮）来自无症状的母亲。我们证实母体CHD7的淋球菌镶嵌性是胎儿CS的遗传原因。我们的研究结果强调了临床分析的重要性，在准确确定父母的状态，在检测CHD7从头变异胎儿CS，因为这项分析对于评估遗传咨询的复发风险具有重要意义.
