Zhao Bowen, Ding Fengjuan, Hou Fei, Jin Hua
Department of Prenatal Diagnosis, Jinan Maternity and Child Care Hospital Affiliated Shandong First Medical University (Jinan Maternity and Child Care Hospital), Jinan, Shandong, China.
Front Pediatr. 2025 Sep 4;13:1655021. doi: 10.3389/fped.2025.1655021. eCollection 2025.
Bainbridge-Ropers syndrome (BRS) is a neurodevelopmental disorder predominantly caused by pathogenic variants in the gene, which have been conventionally considered to occur . This study aimed to investigate the potential role of parental mosaicism in BRS inheritance and its clinical implications for genetic counseling.
Trio-based whole-exome sequencing (WES) was performed on the proband and both parents to identify candidate variants, which were subsequently validated by Sanger sequencing. -targeted ultra-deep sequencing of paternal semen DNA was then carried out to detect low-level mosaicism. Prenatal diagnosis via amniocentesis was used to evaluate transmission of the familial variant.
We definitively diagnosed this family by WES and found the lowest level of paternal mosaicism reported to date, with a peripheral blood variant allele frequency (VAF) of 8.17% and a semen VAF of 15.03%. Prenatal diagnosis at 18 weeks of gestation confirmed that the variant was not detected in this pregnancy.
This study establishes parental chimerism as an important genetic mechanism for -associated disorders and emphasizes the need for ultrasensitive testing in genetic counseling. The findings redefine genetic risk stratification for BRS and provide a basis for accurate family planning based on high-depth sequencing.
班布里奇 - 罗佩斯综合征（BRS）是一种神经发育障碍，主要由基因中的致病变异引起，传统上认为这些变异是随机发生的。本研究旨在探讨亲代嵌合体在BRS遗传中的潜在作用及其对遗传咨询的临床意义。
对先证者及其父母进行基于三联体的全外显子组测序（WES）以鉴定候选变异，随后通过桑格测序进行验证。然后对父系精液DNA进行靶向超深度测序以检测低水平嵌合体。通过羊膜穿刺术进行产前诊断以评估家族性变异的传递。
我们通过WES明确诊断了这个家系，并发现了迄今为止报道的最低水平的父系嵌合体，外周血变异等位基因频率（VAF）为8.17%，精液VAF为15.03%。妊娠18周时的产前诊断证实该变异在本次妊娠中未被检测到。
本研究确立了亲代嵌合现象是与[具体疾病]相关疾病的重要遗传机制，并强调了在遗传咨询中进行超灵敏检测的必要性。这些发现重新定义了BRS的遗传风险分层，并为基于深度测序的准确计划生育提供了依据。
