Yu Qiu-Xia, Zhen Li, Xiao Zhi-Qing, Wen Yun-Jing, Li Dong-Zhi
Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Prenat Diagn. 2025 Feb;45(2):218-222. doi: 10.1002/pd.6705. Epub 2024 Nov 12.
To determine the exome sequencing results in fetuses with bilateral renal agenesis (BRA).
This was a retrospective study of 14 cases with BRA diagnosed on second trimester anatomy ultrasound. All cases underwent invasive prenatal diagnosis. Genetic investigations were performed by chromosomal microarray analysis and trio exome sequencing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, molecular sequencing results, and pregnancy outcomes.
Pathogenic and likely pathogenic variants in three genes (FRAS1, PBX1, and KMT2D) were detected by exome sequencing in 6 (6/14) cases. One gene (FRAS1) is inherited in an autosomal recessive (AR) manner and two (PBX1 and KMT2D) are autosomal dominant (AD); both AD variants were de novo. Only the FRAS1 variants were detected in more than one case. Variants in five cases were believed to be the cause of BRA, and the variants detected in PBX1 and KMT2D were likely the cause of fetal phenotype suggesting that the two genes can present with BRA. The yield of exome sequencing in our series is one third (4/12) after excluding two families with a previous family history.
Fraser syndrome, resulting from FRAS1 variants, is the most common cause of genetic BRA identified in this specific cohort. The determination of genetic etiology will be valuable in the possible choices for pregnancy management and risk assessment of recurrence in future pregnancies.
确定双侧肾缺如（BRA）胎儿的外显子组测序结果。
这是一项对14例在孕中期解剖超声检查中诊断为BRA的病例进行的回顾性研究。所有病例均接受了侵入性产前诊断。通过染色体微阵列分析和三联体外显子组测序进行基因研究。收集并审查了这些病例的临床和实验室数据，包括产妇人口统计学资料、产前超声检查结果、分子测序结果和妊娠结局。
外显子组测序在6例（6/14）病例中检测到三个基因（FRAS1、PBX1和KMT2D）的致病和可能致病变异。一个基因（FRAS1）以常染色体隐性（AR）方式遗传，两个基因（PBX1和KMT2D）以常染色体显性（AD）方式遗传；两个AD变异均为新发。只有FRAS1变异在不止一例中被检测到。五例中的变异被认为是BRA的病因，在PBX1和KMT2D中检测到的变异可能是胎儿表型的病因，这表明这两个基因可导致BRA。在排除两个有家族病史的家庭后，我们系列中外显子组测序的检出率为三分之一（4/12）。
由FRAS1变异导致的弗雷泽综合征是该特定队列中确定的遗传性BRA的最常见病因。确定遗传病因对于未来妊娠管理的可能选择以及复发风险评估具有重要价值。
