Genetic etiology of fetuses with congenital solitary functioning kidney: analysis of 422 cases
10.3760/cma.j.cn113903-20240307-00185
- VernacularTitle:先天性功能性孤立肾胎儿的遗传学病因：422例分析
- Author:
Yang CHEN
1
;
Hongke DING
;
Jian LU
;
Juan ZHU
;
Lijuan LYU
Author Information
1. 广州医科大学研究生院，广州 511436
- Publication Type:Journal Article
- Keywords:
Solitary kidney;
Prenatal diagnosis;
Chromosome aberrations;
Retrospective studies
- From:
Chinese Journal of Perinatal Medicine
2025;28(3):185-193
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology of congenital solitary functioning kidney (CSFK).Methods:This retrospective study included 422 fetuses diagnosed with CSFK by prenatal ultrasound who underwent invasive prenatal genetic testing at Guangdong Women and Children Hospital between January 2015 and February 2023. These CSFK fetuses were classified into different subtypes (unilateral renal agenesis and unilateral multicystic dysplastic kidney) and divided into the isolated group ( n=312) and the non-isolated group ( n=110) based on whether there were other associated abnormalities. The results of G-banding karyotyping, chromosomal microarray analysis (CMA), and whole-exome sequencing (WES) among fetuses with different subtypes or from different groups were analyzed. Statistical analysis was performed using the Chi-square (or Fisher's exact) test and rank-sum test. Results:(1) The median maternal age at the time of invasive prenatal diagnosis was 29 years (range: 18-43 years), and the median gestational age was 25 weeks (range: 17-34 weeks). Among the 422 cases, 234 underwent karyotyping and CMA, 63 underwent CMA and WES, and seven underwent all three tests. Therefore, karyotyping, CMA, and WES were completed in 257, 406, and 70 cases, respectively. (2) The detection rate of chromosomal abnormality by G-banding karyotyping was 1.6% (4/257). Among these four cases, CMA detected no abnormalities in one case with chromosomal mosaicism, while the CMA results were consistent with G-banding karyotyping in three cases with chromosomal structural rearrangements. (3) CMA results: The CNV detection was 8.9% (36/406), with 22 cases being classified as pathogenic/likely pathogenic CNVs. Common CNV loci included 17q12 (five cases), 22q11.21 (five cases), and 16p11.2 (two cases). Fifteen cases (68.2%) were associated with microdeletion syndromes. Nineteen mothers opted for pregnancy termination, two continued the pregnancies, and one was lost to follow-up. (4) Among the 241 cases that underwent both G-banding karyotyping and CMA (including seven cases with all three tests), the positive rates for G-banding karyotyping and CMA were 1.7% (4/241) and 5.8% (14/241), respectively. Compared to G-banding karyotyping, CMA provided an additional diagnostic yield of 4.1% (10/241). (5) Among the 70 cases that underwent family-based WES, 26 (37.1%) showed abnormal results, including 12 pathogenic/likely pathogenic variants and 14 variants of uncertain significance. The positive rateby WES was 17.1% (12/70). Six gene variants (mainly PKD1 and HNF1B variants) were associated with the CSFK phenotype, including five autosomal dominant and one autosomal recessive inheritance. Among the 12 WES-positive cases, six had heterozygous variants and six had compound heterozygous variants. Eight mothers chose to continue the pregnancy, two opted for termination, and two were lost to follow-up. (6) Among the 422 CSFK fetuses, 35 (8.3%) had genetic abnormalities. The highest genetic abnormality rate was observed in CSFK fetuses with isolated urinary system abnormalities (15.1%, 8/53), followed by those with additional non-urinary system abnormalities (12.3%, 7/57), and isolated CSFK fetuses (6.4%, 20/312). The differences among the three groups were statistically significant ( χ2=5.95, P=0.048), but no significant differences were found in pairwise comparisons. Conclusion:The primary genetic etiologies of CSFK fetuses include 17q12 microdeletion syndrome, 22q11.2 microdeletion syndrome, and variants in the PKD1 and HNF1B genes.
