Prenatal Genetic Analysis of Kidney Abnormalities

doi:10.21203/rs.3.rs-2575309/v1

Download PDF

Research Article

Prenatal Genetic Analysis of Kidney Abnormalities

https://doi.org/10.21203/rs.3.rs-2575309/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Objective: To systematically analyze the genetic features of fetal renal abnormalities and the prenatal characteristics of 17q12 microdeletion syndrome.

Methods: We retrospective analysis of fetal diagnosed with renal abnormalities from January 2016 to August 2022. Chromosome test, fetal renal abnormalities and pregnancy outcomes were performed in a descriptive analysis.

Results: 141 patients (4.5%) showed abnormal renal development and 26 patients (26/141) with hyperechogenic kidneys (HCK), 14 (14/26) cases showed chromosomal abnormalities, 12 patients were 17q12 microdeletion syndrome. In addition, there were 14 17q12 microdeletion syndrome among the patients, and 12 fetal had hyperechogenic kidneys (HCK), 7 fetal were verified by couples, 5 fetal had new mutations, and 2 fetal inherited from parents. After excluding patients with HCK, the polycystic kidney has a higher rate of chromosomal abnormalities compared to polycystic renal dysplasia and renal dysplasia. The chromosomal of isolated horseshoe kidney, hydronephrosis, ectopic kidney and unilateral kidney often were normal, and the chromosomal abnormalities rate was increased when combined with other abnormalities.

Conclusion: Fatal HCK was closely related to 17q12 microdeletion syndrome. The chromosome test result of patients with isolated polycystic kidney dysplasia, kidney dysplasia, horseshoe kidney, hydronephrosis, kidney deficiency, and ectopic kidney were mostly normal. Prenatal diagnosis was recommended, specifically in the fetus had non-isolated renal abnormalities. Most patients with normal chromosomes or uncertain clinical significance choose to produce, but adverse pregnancy outcomes were not excluded. This study will provide more data support for fetal renal abnormalities.

17q12 microdeletion syndrome

fetal renal abnormalities

genetic features

prenatal diagnosis

In this study we not only analyzed the relationship between prenatal phenotype and genetics of 17q12 microdeletion syndrome, but also explored the relationship of hyperechogenic kidneys and the chromosomal detection results, fetal renal abnormalities and chromosomal detection results. It provide more convincing data for genetic consultation of prenatal fetal renal abnormalities.

Prenatal ultrasound imaging improves the detection rate of the fetal renal abnormalities, and fetal chromosomal results will affect whether the patient continues the pregnancy. With the wide application of genomic single nucleotide polymorphism array (SNP-Array) and copy number variation sequencing (CNV-Seq) detection, more and more pathogenic variants are diagnosed before birth, the early assessment and clinical management could be realized.[1] The most common prenatal phenotype is renal abnormalities, such as hyperechogenic kidneys (HCK) and polycystic dysplasia kidneys (MCDKs).[2; 3; 4; 5] In addition, the use of Chromosomal Microarray Analysis (CMA) could increase detecting pathogenic CNVs in fetuses with prenatal fetal renal abnormalities, such as polycystic renal dysplasia, renal dysplasia, horseshoe kidney, hydronephrosis, ectopic kidney, etc.[6] Nevertheless. their association with chromosomal abnormalities still needs support from clinical data. According to reports, fatal HCK was closely related to 17q12 microdeletion syndrome. The 17q12 chromosome microdeletion syndrome is rarer caused by the deletion of band 2 of the long arm of chromosome 17, and the incidence was about 1/14,500. The deletion area of 17q12 microdeletion syndrome involve pathogenic genes such as HNF1B and LHX1, leading to a variety of clinical phenotypes, including abnormal renal and urethra development and function, type 5 diabetes, abnormal neurodevelopment, and neuropsychiatric disorders.[7; 8; 9] Studies have shown that most of the chromosome 17q12 microdeletion syndrome results from new-onset mutations, with only about 30% originating from parental inheritance.[7] It is suggested that prenatal testing should be offered to all cases of HCK, with unknown cause.[3] To further clarify the chromosomal profile of prenatal fetal renal abnormalities as well as the prenatal characteristics of the 17q12 microdeletion, 3139 patients were included and analyzed who underwent chromosome examination. Our study will provide more convincing data for genetic consultation of prenatal fetal renal abnormalities.

1.1 Study design and subjects

A total of 3,139 pregnant women including SNP-Array 827 and CNV-Seq 2312 were included from January 2016 to August 2022 at Tianjin Central Obstetrics and Gynecology Hospital. The reasons for chromosome test include Non-invasive Prenatal Testing (NIPT) results suggesting chromosomal abnormalities, and prenatal ultrasound findings showing fetal structural abnormalities. Samples included amniotic fluid obtained by amniocentesis as well as fetal skin from induced labor. Clinical data (including maternal age, fetal ultrasound findings, gestational weeks of amniocentesis), the results of SNP-Array or CNV-Seq tests and pregnancy outcomes were collected. The analysis flow chart was shown in Fig. 1. This study was approved by the Medical Ethics Committee of Tianjin Central Obstetrics and Gynecology Hospital. All the pregnant women signed a written informed consent form.

1.2 The SNP-Seq detection method

The Affymetrix CytoScan 750 K Array Chip contains 200,000 SNP markers and 550,000 CNV markers distributed throughout the human genome with an average density of approximately 1 marker/4 Kb (not covering all sites in the whole chromosome genome), and was used to detect the abnormal chromosome copy number changes (CNV) and loss of heterozygosity (LOH) of clinically meaningful chromosomes in the whole genome, such as microdeletion/microduplication of chromosomes and chromosomal subterminal deletion syndrome. The information of Affymetrix CytoScan 750K Array Chip is from www.Affymetrix.com. Microarray detection is used to screen the change of chromosome copy number at a specific resolution and analyze the samples at the resolution level of 50 Kb/25 marker deletion, 100 Kb/25 marker duplication. Generally, deletion of fragments less than 100Kb and duplication of fragments less than 200Kb are not reported. In addition, the copy number changes that are known to belong to normal polymorphism in the whole genome, chromosome balanced translocation, inversion, insertion and low proportion of chimeras are also not reported.

1.3 The CNV-Seq detection method

Genomic DNA was extracted using the DNeasy Blood and Tissue Kit (Qiagen, Germany). The concentration and purity of the genomic DNA were determined by Qubit 2.0 fluorometer. CNV-Seq was detected through Hi Seq 2000 platform (Illumina, United States), with 36 bp single-end sequencing at 0.1x depth. A total of 5 million raw sequencing reads were obtained, and the resolution of CNV detection was about 100 Kb.

1.4 Results analysis

According to the standards and guidelines of the American Society of Medical Genetics (American College of Medical Genetics, ACMG), and with reference to the DECIPHER, DGV, ISCA, Clingen, Gene Reviews, and online human Mendelian genetics (Online Mendelian Inheritance in Man, OMIM) databases, the results were divided into three categories: pathogenic, benign, and unclear clinical significance.

1.5 Statistical analysis

Statistical analyses were carried out using SPSS 27.0 (Chicago, IL, United States). The quantitative data conforming to the normal distribution were represented in the mean ± standard deviation format, and the single factor mean value analysis was conducted for the gestational age.

1 Analysis of chromosome screening results of prenatal hyperechogenic

To analyze the results of chromosomal detection of HCK, 3139 patients were screened with amniocentesis for SNP or CNV-Seq testing, 141 patients (4.5%) showed abnormal renal development and 26 patients (26/141) with HCK, including 10 IHCK and 16 HCK combined with other abnormalities(Non-isolated HCK, NIHCK); in the 10 cases of IHCK, 6 cases had chromosomal abnormalities, all of which were 17q12 microdeletion syndrome, and 4 cases had normal chromosomes; eight of the 16 cases with NIHCK had chromosomal abnormalities, including six cases have 17q12 microdeletion syndrome, one has trisomy 13, one has trisomy 21, and eight other cases had normal chromosomes. The above patients were followed up, and the results showed that among the patients with IHCK after removing the three patients lost to follow-up, more than 50% (4/7) of the patients chose to give birth regardless of whether the chromosome examination results were normal, and one newborn with biliary atresia; after removing 5 cases lost to follow-up, in patients with NIHCK, if the chromosome test results are abnormal, most of the patients are selected for labor induction (5/6), and if the chromosome test results are normal, more than 50% (3/5) of the patients choose the birth. Among the productive patients, one patient was autistic at 2 years of age (Table 1).

Table 1

Chromosomal test and pregnancy outcomes of prenatal hyperechogenic kidneys
	Chromosome abnormalities			Chromosomes normal
	Induction	Term birth	Lost to follow up	Induction	Term birth	Lost to follow up
IHCK (n = 10)	2	2^#1	2	1	2	1
NIHCK (n = 16)	5	1	2	2	3^#2	3
IHCK: Isolated hyperechogenic kidneys; NIHCK: Non-isolated hyperechogenic kidneys;#1: One of the two patients had postnatal biliary atresia; #2: One of them was autistic after birth

2 Analysis of 17q12 microdeletion syndrome in prenatal diagnostic chromosomal screening

Of the 3139 fetuses with paracentesis and CNV-Seq detection before delivery, 14 fetuses were diagnosed as 17q12 microdeletion syndrome, accounting for 0.4% (14/3139) of pathogenic chromosomal abnormalities. The results of ultrasound imaging during pregnancy displayed that 14 patients with 17q12 microdeletion syndrome were all related to renal abnormalities, 12 patients (12/14) showed HCK, 1 patient suffered from fetal hydronephrosis with multiple renal cysts and mild polyhydramnios, and 1 patient had renal deficiency with single umbilical artery.

Furthermore, the ultrasound findings of 12 patients with HCK showed that 6 (6/12) had isolated hyperechogenic kidneys (IHCK) and the other 6 (6/12) had other renal abnormal phenotypes (Table 1). Meanwhile, CNV-Seq detection results revealed that the size of deletion fragments of 14 fetuses with 17q12 microdeletion syndrome were 1.4 ~ 1.7 Mb and all of them contained the HNF1B gene. The average age of the patients was 28.7 ± 1.3 years old, and the average gestational age was 27.3 ± 1.2 weeks, 5 cases were new mutations, 1 case was inherited from the father, 1 case was inherited from the mother, 4 cases were not verified by couples, and 2 cases were lost to follow-up (Table 2).

Table 2

Prenatal 17q12 microdeletion syndrome
Prenatal Ultrasound Results		GA	Pregnancy Outcome
IHCK(n = 6)			Induction(4/6) Term birth: Normal(1/6) Term birth: Biliary atresia (1/6)
NIHCK n = 6	Right hydronephrosis and polycystic dysplasia (1/6)	20 + 2	Induction
	Multiple renal cysts in the left kidney (1/6)	29 + 6	Term birth, Normal
	Long bone of GA is less than GA (1/6)	32 + 6	Lost to follow up
	Broadening of the ventricle (1/6)	29 + 1	Induction
	Polycystic dysplasia (1/6)	20 + 1	Induction
	Hydronephrosis (1/6)	29 + 4	Lost to follow up
Other abnormalities n = 2	Hydronephrosis, multiple renal cysts and mild excessive amniotic fluid (1/6)	27 + 1	Induction
Other abnormalities n = 2	Renal deficiency, single umbilical artery (1/6)	24 + 1	Induction
GA: Gestational age; IHCK: Isolated hyperechogenic kidneys; NIHCK: Non-isolated hyperechogenic kidneys

3 Analysis of the chromosome detection results of other fetal renal abnormalities

In order to further analyze the chromosome detection of other fetal renal abnormalities, statistical analysis was conducted after excluding patients with HCK (Table 3). As shown in Table 3, it includes chromosome examination results and pregnancy outcomes for different kidney abnormalitiesi. In summary, the chromosome test result of patients with isolated polycystic kidney dysplasia, kidney dysplasia, horseshoe kidney, hydronephrosis, kidney deficiency, and ectopic kidney were mostly normal. But the chromosome of the non-isolated patients often was abnormal, such as reproductive organ abnormalities, ventricular septal defects, etc., especially with HCK. The rate of chromosomal abnormalities in fetal polycystic kidney was higher compared to the above-mentioned fetal kidney diseases, which was only inferior to fetal HCK. However, the results of chromosomes test were not consistent. Most patients with normal chromosomes or uncertain clinical significance choose to produce, but adverse pregnancy outcomes were not excluded.

Table 3

Chromosomal test and pregnancy outcomes of other prenatal fetal renal abnormalities
		Chromosome results		Pregnancy outcome
		Normal	Abnormal	Induction	Term birth	Lost to follow up
Polycystic kidney	Isolated (n = 14)	10	4	5	6	3
Polycystic kidney	Non-isolated (n = 5)	2	3	3	2	0
Renal cystic dysplasia	Isolated (n = 20)	19	1	3	14	3
Renal cystic dysplasia	Non-isolated (n = 5)	4	1	0	4	1
Renal hypodysplasia	Isolated (n = 6)	6	0	3	1	2
Renal hypodysplasia	Non-isolated (n = 7)	6	1	3	4	0
Horseshoe kidney	Isolated (n = 1)	1	0	1	0	0
Horseshoe kidney	Non-isolated (n = 4)	3	1	2	2	0
Hydronephrosis	Isolated (n = 3)	3	0	0	3	0
Hydronephrosis	Non-isolated (n = 16)	11	5	4	10	2
Unilateral kidney	Isolated (n = 6)	6	0	1	5	0
Unilateral kidney	Non-isolated (n = 9)	5	4	4	5	0
Renal ectopia	Isolated (n = 0)	0	0	0	0	0
Renal ectopia	Non-isolated (n = 9)	9	1	2	7	1
Duplex kidney	Isolated (n = 4)	4	0	1	3	0
Duplex kidney	Non-isolated (n = 6)	6	0	1	2	3

The basic principle of ultrasound imaging is related to the physical characteristics of ultrasonic waves and a variety of physical phenomena generated by human tissue to incident ultrasonic waves[10] Hyperechogenic kidneys might be enhanced renal fibrosis. Our study found a total of 26 patients suffered from HCK, including 10 patients with isolated HCK, 6(6/10) patients with 17q12 microdeletion syndrome, and 4 cases with normal chromosomes. Among 16 cases of non-isolated HCK, 8 fetus had chromosomal abnormalities, including 6 cases of 17q12 microdeletion syndrome, 1 case of trisomy 13, 1 case of trisomy 21, and 8 cases of normal chromosomes. The correlation between HCK and trisomy 13 and 21 is still unclear. In this study, chromosomal analysis showed that the size of deletion fragments in the fetuses with 17q12 microdeletion syndrome ranged from 1.4 to 1.7 Mb, containing the HNF1B gene. It has been found that HNF1B mutation is the major cause of prenatal hyperechoic kidney with normal size. The patients with HNF1B mutation often suffered from atypical hyperplasia with or without tubular fibrosis.[2; 4; 8] Besides, the reclassification of all previously reported intragenic HNF1B variants provided a novel perspective on the mutational spectrum.[11] Another key gene, LHX1, is involved by the 17q12 microdeletion, which is known to be critical for the normal development and function of the brain, which validated in C57BL/6N.[5; 12] A small number of children with 17q12 microdeletion syndrome suffer from autism and schizophrenia.[13; 14] However, there is a lack of effective prenatal assessment of fetal neuropsychiatric development, and the neuropsychiatric deficits associated with 17q12 deletion are a major challenge for prenatal counseling.

The main clinical features of 17q12 microdeletion syndrome are structural or functional abnormalities in the kidney and urethra, type 5 diabetes, and neurodevelopmental or neuropsychiatric disorders.[15] It has been reported that 11 cases of 17q12 microdeletion fetus have enhanced renal echo ultrasound, 2 cases also accompanied by kidney enlargement,[4] 88% of 17q12 microdeletion fetal prenatal ultrasound enhanced renal echo, but no obvious change in kidney size.[7] In our study, 12 cases showed enhanced renal echo among 14 patients with 17q12 microdeletion syndrome, which was consistent with the above report. Further analysis of the ultrasonic findings of 12 patients with 17q12 microdeletion syndrome showed that 6 cases had isolated enhanced renal echo, and the other 6 cases were combined with other abnormal renal phenotypes. It was reported that genetic etiologies (ARPKD, ADPKD, BBS, HNF1B-related disorder, Beckwith-Wiedemann syndrome, tubular dysgenesis, familial nephroblastoma, and cytogenetic abnormalities) account for approximately half of prenatally isolated fetal hyperechogenic kidneys; there are few neonatal deaths and short-term renal outcomes once excluded genetic etiologies.[16] Other prenatal ultrasound findings of the 17q12 microdeletion syndrome included congenital diaphragmatic hernia, persistent left superior vena cava, intestinal obstruction, intrauterine growth retardation, duodenal atresia, etc.[17] In our study, we found that there were patients who suffered from hyperechogenic kidneys combined with ventricle widening or single umbilical artery, one patient was diagnosed as hydronephrosis combined with multiple renal cysts and mild amniotic fluid bias, and one patient had unilateral kidney combined with single umbilical artery. Consequently, 17q12 microdeletion syndrome often combined with hyperechogenic kidneys or other abnormalities. In practice, abnormal performance still needs the support of clinical data.

Once ultrasound imaging showed fetal renal abnormalities, an interventional prenatal diagnosis was usually considered. But a growing number of studies revealed that some renal abnormalities are closely related to chromosomal abnormalities, but some are not. Renal cystic disease may be unilateral or bilateral and present as single or multiple cysts. Various cystic diseases could transform into chronic kidney disease (CKD), including renal failure and liver disease, or life-threatening.[18] Accordingly, the detailed evaluation of renal cystic disease in the fetus plays a vital role in its prognosis. Hydronephrosis or uronephrosis, polycystic kidney disease, and renal hypodysplasia are the most common fetal manifestations of urinary system abnormalities. Approximately 10.1% of them showed abnormal performance in genetic testing.[19] CNVs were most common in the fetal renal ectopia (9.5%) and were not detectable in the horseshoe kidney or isolated duplex kidney.[20] Our study revealed that the rate of chromosomal abnormalities was higher in polycystic kidney than that in renal polycystic dysplasia. It was reported that a substantial proportion of renal polycystic dysplasia were associated with pathogenic CNVs,[21] which was consistent with our report. We also found that the results of chromosomal test for patients with isolated horseshoe kidney, hydronephrosis and unilateral kidney were all normal, but the detection rate of chromosomal abnormalities was relatively higher when patients suffered from other abnormalities. All the patients with renal ectopia had other abnormalities, but the chromosomal test results showed that most of them were normal, only one patient with hydronephrosis showed abnormalities. With the advent of high-resolution ultrasound devices, imaging of the renal system in early fetal pregnancy may become an important means of examination.[22] Hence, once renal abnormalities are found before delivery, it is important to determine whether they are related to chromosomal abnormalities for pregnancy outcome.

This study also has some limitations. First, the number of cases of 17q12 microdeletion syndrome is small, some of the abnormal CNV-seq or SNP-Array test results are not verified by parents, and there is also a loss to follow-up. However, for fetal patients with isolated horseshoe kidney, hydronephrosis, unilateral kidney, renal ectopia, and duplex kidney, whether they choose to continue pregnancy is often correlated with the test results of CNV-seq or SNP-Array. If the disease is clear, most people choose to induce labor. If the clinical significance is unclear or the disease is not pathogenic, most people choose to continue pregnancy, with a good prognosis, but adverse pregnancy outcomes are not excluded. Second, autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease caused by mutations in PKHD1. It is important to differentiate between 17q12 microdeletion syndrome and ARPKD, because they differ significantly in inheritance patterns, renal prognosis, and extrarenal manifestations.[23; 24] Whereas CNV detects deletions and repeats over 100 kb, further whole-exome sequencing should be used if ARPKD should is diagnosed.[25]

In conclusion, fetal HCK was closely related to 17q12 microdeletion syndrome, renal cystic changes had a high rate of chromosomal abnormalities. Prenatal invasive diagnosis should be considered if prenatal ultrasonography finds that the fetus has HCK or renal cystic changes. Chromosomes detection of horseshoe kidney, hydronephrosis, and unilateral kidney were normal. The detection rate of chromosomal abnormalities is relatively high when combined with other abnormalities. All patients with renal ectopia had other structural abnormalities, but only one patient with hydronephrosis suffered from chromosomal abnormalities. Most of the chromosomal detection results displayed that patients with unclear clinical significance or non-pathopoiesia chose to give birth and had a good prognosis, but adverse pregnancy outcomes were not excluded. For these patients, attention should be paid to the development of the fetal kidney and whether there are other structural abnormalities, and a comprehensive evaluation should be done for invasive prenatal diagnosis or postnatal reexamination. The specific relationship between chromosomal abnormalities and renal lesions remains to be investigated. Our study provides more data support for the correlation between HCK and 17q12 microdeletion syndrome, fetal renal abnormalities and chromosomal abnormalities, and lays a theoretical foundation for the prenatal diagnosis of fetal renal tissue abnormalities.

Funding

This study was supported by National Natural Science Foundation of China (82001579), Tianjin Key Medical Discipline (Specialty) Construction Project (TJWJ2021QN053), Open Fund of Tianjin Central Hospital of Gynecology Obstetrics/Tianjin Key Laboratory of human development and reproductive regulation (2022XH10).

Author Contributions

Shen Yongmei, Li Yaqi and Zhao Xiaomin: conceptualization, design, writing original draft; Li Wen and Zhang Lei: chromosomal and Ultrasonic testing; Yao Liying and Cao Jiasong: methodology and data analysis; Li Shanshan and Wei Zhuo: data curation, editing; Chang Ying: conceptualization, supervision. All authors read and approved the final manuscript.

Conflict of interest：

The authors have no relevant financial or non-financial interests to disclose.

Authors: Yongmei Shen, Yaqi Li, Xiaomin Zhao, Wen Li, Lei Zhang, Liying Yao, Jiasong Cao, Shanshan Li, Zhuo Wei, Ying Chang

Deng L, Liu Y, Yuan M, et al (2022) Prenatal diagnosis and outcome of fetal hyperechogenic kidneys in the era of antenatal next-generationsequencing. Clin Chim Acta 528:16-28. doi:10.1016/j.cca.2022.01.012
Jiang YL, Qi QW, Zhou XY, et al (2017) Prenatal diagnosis of 17q12 microdeletion syndrome in fetal renal abnormalities. Zhonghua Fu Chan Ke Za Zhi 52:662-668. doi:10.3760/cma.j.issn.0529-567X.2017.10.004
Jones GE, Mousa HA, Rowley H, et al (2015) Should we offer prenatal testing for 17q12 microdeletion syndrome to all cases with prenatally diagnosed echogenic kidneys? Prenatal findings in two families with 17q12 microdeletion syndrome and review of the literature. Prenat Diagn 35:1336-1341. doi:10.1002/pd.4701
Jing X-Y, Huang L-Y, Zhen L, et al (2019) Prenatal diagnosis of 17q12 deletion syndrome: a retrospective case series. J Obstet Gynaecol 39:323-327. doi:10.1080/01443615.2018.1519693.
Zhou C-X, Zhu X-Y, Zhu Y-J, et al (2021) Prenatal features of 17q12 microdeletion and microduplication syndromes: A retrospective case series. Taiwan J Obstet Gynecol 60:232-237. doi:10.1016/j.tjog.2021.01.001
Li S, Han X, Wang Y, et al (2019) Chromosomal microarray analysis in fetuses with congenital anomalies of the kidney and urinary tract: A prospective cohort study and meta-analysis. Prenat Diagn 39:165-174. doi:10.1002/pd.5420
Zhang Z, Pan L, Chen K, et al (2021) Prenatal ultrasound features and genetic analysis for 17q12 microdeletion syndrome. Zhong Nan Da Xue Xue Bao Yi Xue Ban 46:1370-1374. doi:10.11817/j.issn.1672-7347.2021.210412
Cleper R, Reches A, Shapira D, et al (2021) Improving renal phenotype and evolving extra-renal features of 17q12 deletion encompassing the gene. Transl Pediatr 10:3130-3139. doi:10.21037/tp-21-386
Li H, Chen C, Tu J, et al (2022) Two cases of fetal hyperechogenic kidneys who had gene variation. Clin Nephrol 98:309-316. doi:10.5414/CN110895
Prabhu M, Kuller JA, Biggio JR (2021) Society for Maternal-Fetal Medicine Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester: (Replaces Consults #10, Single umbilical artery, October 2010; #16, Isolated echogenic bowel diagnosed on second-trimester ultrasound, August 2011; #17, Evaluation and management of isolated renal pelviectasis on second-trimester ultrasound, December 2011; #25, Isolated fetal choroid plexus cysts, April 2013; #27, Isolated echogenic intracardiac focus, August 2013). Am J Obstet Gynecol 225:B2–B15. doi:10.1016/j.ajog.2021.06.079
Vasileiou G, Hoyer J, Thiel CT, et al (2019) Prenatal diagnosis of HNF1B-associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome? Prenat Diagn 39:1136-1147. doi:10.1002/pd.5556
Warren EB, Briano JA, Ellegood J, et al (2022) Mouse Model of 17q12 deletion shows defects in craniofacial, brain and kidney development, and in glucose homeostasis. Dis Model Mech. doi:10.1242/dmm.049752
Dima DC, Adams R, Linden SC, et al (2020) Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk. Transl Psychiatry 10:324. doi:10.1038/s41398-020-00998-w
Clissold RL, Shaw-Smith C, Turnpenny P, et al (2016) Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. Kidney Int 90:203-211. doi:10.1016/j.kint.2016.03.027
Cai M, Lin M, Guo N, et al (2022) Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome. Front Pediatr 10:910497. doi:10.3389/fped.2022.910497
Digby EL, Liauw J, Dionne J, et al (2021) Etiologies and outcomes of prenatally diagnosed hyperechogenic kidneys. Prenat Diagn 41:465-477. doi:10.1002/pd.5883
Țuțulan-Cuniță A, Pavel AG, Dimos L, et al (2021) Phenotypic Variability of 17q12 Microdeletion Syndrome - Three Cases and Review of Literature. Balkan J Med Genet 24:71-82. doi:10.2478/bjmg-2021-0025
Raina R, Chakraborty R, Sethi SK, et al (2021) Diagnosis and Management of Renal Cystic Disease of the Newborn: Core Curriculum 2021. Am J Kidney Dis. 78(1):125-141. doi:10.1053/j.ajkd.2020.10.021
Zeng S, Wang L, Luo S, et al. Genetic testing and pregnancy outcome of 337 fetuses with urinary system anomalies. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019;36(4):306-309. doi:10.3760/cma.j.issn.1003-9406.2019.04.004
Lin S, Shi S, Huang L, et al (2019) Is an analysis of copy number variants necessary for various types of kidney ultrasound anomalies in fetuses? Mol Cytogenet 12:31. doi:10.1186/s13039-019-0443-3
Xi Q, Zhu X, Wang Y, et al (2016) Copy number variations in multicystic dysplastic kidney: update for prenatal diagnosis and genetic counseling. Prenat Diagn 36:463-468. doi:10.1002/pd.4807
Jelin A (2021) Renal agenesis. Am J Obstet Gynecol. 225:B28-B30. doi:10.1016/j.ajog.2021.06.048
Ding W-P, Li N, Chen M (2020) Ultrasound Screening of Fetal Anomalies at 11–13+6 Weeks. Maternal-Fetal Medicine 2(3):175-180. doi:10.1097/FM9.0000000000000045
Nakamura M, Kanda S, Kajiho Y, et al (2021) A case of 17q12 deletion syndrome that presented antenatally with markedly enlarged kidneys and clinically mimicked autosomal recessive polycystic kidney disease. CEN Case Rep 10:543-548. doi:10.1007/s13730-021-00604-y
Liu L, Li J, Li Y, et al (2022) Genetic diagnosis of common fetal renal abnormalities detected on prenatal ultrasound. Prenat Diagn 42:894-900. doi:10.1002/pd.6154

Download PDF

Version 1

posted

You are reading this latest preprint version

Prenatal Genetic Analysis of Kidney Abnormalities

Status:

Version 1

Abstract

Figures

What Does This Study Adds To The Clinical Work

Introduction

Methods

1.1 Study design and subjects

1.2 The SNP-Seq detection method

1.3 The CNV-Seq detection method

1.4 Results analysis

1.5 Statistical analysis

Results

1 Analysis of chromosome screening results of prenatal hyperechogenic

2 Analysis of 17q12 microdeletion syndrome in prenatal diagnostic chromosomal screening

3 Analysis of the chromosome detection results of other fetal renal abnormalities

Discussion

Declarations

References

Status:

Version 1