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Whole-exome sequencing for prenatal diagnosis of fetuses with congenital anomalies of the kidney and urinary tract.
Nephrol Dial Transplant 2017; 32(10):1665-1675ND

Abstract

Background

In the absence of cytogenetic abnormality, fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with/without other structural anomalies show a higher likelihood of monogenic causes; however, defining the underlying pathology can be challenging. Here, we investigate the value of whole-exome sequencing (WES) in fetuses with CAKUT but normal findings upon karyotyping and chromosome microarray analysis.

Methods

WES was performed on DNA from the cord blood of 30 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 23 cases, sequencing was initially performed on fetal DNA only; for the remaining seven cases, the trio of fetus, mother and father was sequenced simultaneously.

Results

Of the 30 cases, pathogenic variants were identified in 4 (13%) (UMOD, NEK8, HNF1B and BBS2) and incidental variants in 2 (7%) (HSPD1 and GRIN2B). Furthermore, two of the above four cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/22 (9.1%) for isolated CAKUT and 2/8 (25%) for CAKUT with other abnormalities.

Conclusions

Applying WES to the prenatal diagnostic approach in CAKUT fetuses with or without other anomalies allows for an accurate and early etiology-based diagnosis and improved clinical management. To expedite interpretation of the results, trio sequencing should be employed; however, interpretation may nevertheless be compromised by incomplete coverage of all relevant genes.

Authors+Show Affiliations

Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Eugenic and Perinatal Institute, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Eugenic and Perinatal Institute, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Eugenic and Perinatal Institute, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Eugenic and Perinatal Institute, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Eugenic and Perinatal Institute, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28387813

Citation

Lei, Ting-Ying, et al. "Whole-exome Sequencing for Prenatal Diagnosis of Fetuses With Congenital Anomalies of the Kidney and Urinary Tract." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 32, no. 10, 2017, pp. 1665-1675.
Lei TY, Fu F, Li R, et al. Whole-exome sequencing for prenatal diagnosis of fetuses with congenital anomalies of the kidney and urinary tract. Nephrol Dial Transplant. 2017;32(10):1665-1675.
Lei, T. Y., Fu, F., Li, R., Wang, D., Wang, R. Y., Jing, X. Y., ... Liao, C. (2017). Whole-exome sequencing for prenatal diagnosis of fetuses with congenital anomalies of the kidney and urinary tract. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 32(10), pp. 1665-1675. doi:10.1093/ndt/gfx031.
Lei TY, et al. Whole-exome Sequencing for Prenatal Diagnosis of Fetuses With Congenital Anomalies of the Kidney and Urinary Tract. Nephrol Dial Transplant. 2017 Oct 1;32(10):1665-1675. PubMed PMID: 28387813.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Whole-exome sequencing for prenatal diagnosis of fetuses with congenital anomalies of the kidney and urinary tract. AU - Lei,Ting-Ying, AU - Fu,Fang, AU - Li,Ru, AU - Wang,Dan, AU - Wang,Rong-Yue, AU - Jing,Xiang-Yi, AU - Deng,Qiong, AU - Li,Zhou-Zhou, AU - Liu,Ze-Qun, AU - Yang,Xin, AU - Li,Dong-Zhi, AU - Liao,Can, PY - 2016/10/30/received PY - 2017/01/20/accepted PY - 2017/4/8/pubmed PY - 2018/3/1/medline PY - 2017/4/8/entrez KW - BBS2 KW - NEK8 KW - UMOD KW - congenital anomalies of the kidney and urinary tract KW - monogenic causes SP - 1665 EP - 1675 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol. Dial. Transplant. VL - 32 IS - 10 N2 - Background: In the absence of cytogenetic abnormality, fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with/without other structural anomalies show a higher likelihood of monogenic causes; however, defining the underlying pathology can be challenging. Here, we investigate the value of whole-exome sequencing (WES) in fetuses with CAKUT but normal findings upon karyotyping and chromosome microarray analysis. Methods: WES was performed on DNA from the cord blood of 30 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 23 cases, sequencing was initially performed on fetal DNA only; for the remaining seven cases, the trio of fetus, mother and father was sequenced simultaneously. Results: Of the 30 cases, pathogenic variants were identified in 4 (13%) (UMOD, NEK8, HNF1B and BBS2) and incidental variants in 2 (7%) (HSPD1 and GRIN2B). Furthermore, two of the above four cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/22 (9.1%) for isolated CAKUT and 2/8 (25%) for CAKUT with other abnormalities. Conclusions: Applying WES to the prenatal diagnostic approach in CAKUT fetuses with or without other anomalies allows for an accurate and early etiology-based diagnosis and improved clinical management. To expedite interpretation of the results, trio sequencing should be employed; however, interpretation may nevertheless be compromised by incomplete coverage of all relevant genes. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/28387813/Whole_exome_sequencing_for_prenatal_diagnosis_of_fetuses_with_congenital_anomalies_of_the_kidney_and_urinary_tract_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfx031 DB - PRIME DP - Unbound Medicine ER -