Molecular Genetics and Genomics

, Volume 294, Issue 2, pp 493–500 | Cite as

Noncoding rare variants of TBX6 in congenital anomalies of the kidney and urinary tract

  • Shuangshuang Dong
  • Chunyan Wang
  • Xueping Li
  • Qian Shen
  • Xiaoyi Fu
  • Mingyan Wu
  • Chengcheng Song
  • Nan Yang
  • Yanhua Wu
  • Hongyan Wang
  • Li Jin
  • Hong XuEmail author
  • Feng ZhangEmail author
Original Article


Congenital anomalies of the kidney and urinary tract (CAKUT) are a wide range of congenital structural renal defects. CAKUT is the leading cause of chronic renal failure and end-stage renal disease in children. Studies in humans and animal models have confirmed the large genetic contribution to CAKUT. The previous evidence suggested that human TBX6 coding mutations might cause CAKUT via gene-dosage insufficiency. However, the potential involvement of TBX6 noncoding mutations in CAKUT remains to be elucidated. Here, we described DNA sequencing and copy-number analysis of TBX6 in 269 Chinese subjects with CAKUT. Interestingly, we identified two heterozygous noncoding variants of TBX6 in sporadic subjects with CAKUT: one is c.769-7delT, from a subject with duplex renal and collecting system, and the other is a 3′ untranslated region (3′-UTR) variant (c.1392C>T) from a subject with unilateral renal hypoplasia. These two TBX6 noncoding variants are novel and extremely rare, respectively, in human populations archived in the ExAC database. The mini-gene splicing assay showed that the TBX6 c.769-7delT variant significantly reduced the splicing efficiency of TBX6 intron 5 when compared to the wild-type control. In this work, we identified a novel splicing variant of TBX6 in human CAKUT. Our experimental observations suggested that the TBX6 noncoding variant can affect gene expression and may potentially be involved in human CAKUT.


CAKUT Gene dosage Noncoding variant TBX6 



We thank Drs. Ting Ni and Hongbo Nie for their kind assistance with cell experiments. This work was supported by National Natural Science Foundation of China (31771396, 31625015, 31521003, and 81670609), Shanghai Medical Center of Key Programs for Female Reproductive Diseases (2017ZZ01016), and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

The protocol of this study was approved by the Institutional Review Board committees at School of Life Sciences and Children’s Hospital of Fudan University.

Informed consent

Signed parental/guardian consents were obtained from all individual participants included in the study.

Supplementary material

438_2018_1522_MOESM1_ESM.pdf (351 kb)
Supplementary material 1 (PDF 350 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Life SciencesFudan UniversityShanghaiChina
  2. 2.Institute of Metabolism and Integrative BiologyFudan UniversityShanghaiChina
  3. 3.Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghaiChina
  4. 4.Department of NephrologyChildren’s Hospital of Fudan UniversityShanghaiChina
  5. 5.Shanghai Kidney Development and Pediatric Kidney Disease Research CenterShanghaiChina

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