Shi Wei-Hui, Ye Mu-Jin, Chen Song-Chang, Zhang Jun-Yu, Chen Yi-Yao, Zhou Zhi-Yang, Qin Ning-Xin, Zhou Xuan-You, Xu Nai-Xin, Jiang Zi-Ru, Lin Jing, Huang He-Feng, Xu Chen-Ming
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.
Front Genet. 2021 Feb 9;12:633003. doi: 10.3389/fgene.2021.633003. eCollection 2021.
Alport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in at Xq22 accounts for 80-85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling.
Prenatal diagnoses were performed by amplifying targeted regions of . Targeted next-generation sequencing (NGS)-based haplotype analysis or karyomapping was performed in two patients. Pregnancy outcomes in the three patients were collected and analyzed. Published Alport syndrome cases were searched in Pubmed and Embase.
Prenatal diagnoses in two cases showed one fetus harbored the same pathogenic mutation as the proband and the other was healthy. The couple with an affected fetus and the patient with a family history of Alport syndrome chose to take the preimplantation genetic testing (PGT) procedure. One unaffected embryo was transferred to the uterus, and a singleton pregnancy was achieved, respectively. Two patients presented non-nephrotic range proteinuria (<3 g/24 h) during pregnancy and the three cases all delivered at full-term. However, published Alport cases with chronic kidney disease or proteinuria during pregnancy were came with a high rate (75%) of adverse maternal and fetal outcomes.
The PGT procedure performed in this study was proven to be practicable and might be expanded to be applied in other monogenic diseases. Moderate or severe renal impairments in Alport syndrome were strongly associated with adverse maternal and fetal outcomes, and baseline proteinuria was a potential predictor for pregnancy outcomes of Alport syndrome as other kidney diseases.
Alport综合征是一种单基因肾病，其特征为进行性出血性肾炎、感音神经性听力丧失和眼部异常。位于Xq22的基因突变占X连锁Alport综合征患者的80 - 85%。三对夫妇因产前或孕前咨询转诊至我们的生殖遗传学诊所。
通过扩增相关基因的靶向区域进行产前诊断。对两名患者进行了基于靶向新一代测序（NGS）的单倍型分析或核型定位分析。收集并分析了这三名患者的妊娠结局。在Pubmed和Embase中检索已发表的Alport综合征病例。
两例产前诊断显示，一个胎儿携带与先证者相同的致病突变，另一个胎儿健康。携带患病胎儿的夫妇以及有Alport综合征家族史的患者选择了胚胎植入前遗传学检测（PGT）程序。分别将一个未受影响的胚胎移植到子宫内，均实现了单胎妊娠。两名患者在孕期出现非肾病范围蛋白尿（<3 g/24 h），三例均足月分娩。然而，已发表的孕期患有慢性肾病或蛋白尿的Alport病例母婴不良结局发生率较高（75%）。
本研究中实施的PGT程序被证明是可行的，可能会扩展应用于其他单基因疾病。Alport综合征中的中度或重度肾功能损害与母婴不良结局密切相关，基线蛋白尿与其他肾病一样，是Alport综合征妊娠结局潜在的预测指标。
