Yang Huiru, Zhang Jingzhi, Tang Yao, Zhong Qiang, Qian Wen, Wang Zhengrong, Zhou Zunlun, Zhang Zulong, Pan Wei
Department of Nephrology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Prenatal Diagnosis Center in Guizhou Province, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Pediatr Res. 2025 Jan;97(1):273-279. doi: 10.1038/s41390-024-03178-4. Epub 2024 Jun 7.
Congenital unilateral renal agenesis (URA) is a kind of rare birth defect during fetal development with varies clinical phenotypes. The pathogenesis and the relationship between gene and phenotype are still unclear.
Ten URA fetuses were followed up after birth using postnatal renal ultrasound examination to confirm the diagnosis with nine children were URA and one was Renal Ectopy (RE). Trio- WES, CNV- seq were performed with the 10 children and their close relatives.
There were 3 heterozygous variants of CHD7, PROKR2 and NRIP1 genes were identified in 3 children, respectively. CHD7 (c.2663T>C, p.M888T) is classified as likely pathogenic (LP), PROKR2 (c.685G>C, p.G229R) and NRIP1 (c.2705T>G, p.F902C) are classified as variants of uncertain significance (VUS). CHD7 (c.2663T>C, p.M888T) and PROKR2 (c.685G>C, p.G229R) as URA-related genes may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS), and 3D-protein structure prediction revealed that the two variants may affect the stability in the CHD7 protein or PROKR2 protein, separately. The RE-related gene NRIP1 (c.2705T>G, p.F902C) may be causative of congenital anomalies of the kidneys and urinary tract (CAKUT).
Identification of these variants can in exploring the etiology of URA or RE and improve the level of genetic counseling.
We performed trio-whole-exome sequencing (trio- WES) and copy number variation sequencing (CNV- seq) in 10 children, including 9 children with Unilateral Renal Agenesis and 1 with Renal Ectopy after birth. The possible pathogenic genes of URA can be screened using prenatal and postnatal diagnosis of URA fetuses and gene detection after birth. Future studies evaluating this association may lead to a better understanding of URA and elucidate exploring the etiology of URA or RE and improve the level of genetic counseling.
先天性单侧肾发育不全（URA）是胎儿发育过程中一种罕见的出生缺陷，具有多种临床表型。其发病机制以及基因与表型之间的关系仍不清楚。
对10例URA胎儿出生后进行随访，采用产后肾脏超声检查确诊，其中9例为URA，1例为肾异位（RE）。对这10名儿童及其近亲进行三联全外显子测序（Trio-WES）和拷贝数变异测序（CNV-seq）。
分别在3名儿童中鉴定出CHD7、PROKR2和NRIP1基因的3个杂合变异。CHD7（c.2663T>C，p.M888T）被分类为可能致病（LP），PROKR2（c.685G>C，p.G229R）和NRIP1（c.2705T>G，p.F902C）被分类为意义未明的变异（VUS）。CHD7（c.2663T>C，p.M888T）和PROKR2（c.685G>C，p.G229R）作为与URA相关的基因，可能与特发性低促性腺激素性性腺功能减退（IHH）或CHARGE综合征（CS）有关，三维蛋白质结构预测显示这两个变异可能分别影响CHD7蛋白或PROKR2蛋白的稳定性。与RE相关的基因NRIP1（c.2705T>G，p.F902C）可能是先天性肾脏和尿路畸形（CAKUT）的病因。
鉴定这些变异有助于探索URA或RE的病因，并提高遗传咨询水平。
我们对10名儿童进行了三联全外显子测序（Trio-WES）和拷贝数变异测序（CNV-seq），其中包括9例出生后单侧肾发育不全儿童和1例肾异位儿童。通过对URA胎儿进行产前和产后诊断以及出生后基因检测，可以筛选出URA可能的致病基因。未来评估这种关联的研究可能会更好地理解URA，并有助于阐明URA或RE的病因，提高遗传咨询水平。
