Abstract
Study Objective
The purpose of this study was to determine if there are any genetic changes with whole-exome
sequencing associated with distal vaginal atresia.
Design
This was a retrospective genetics study of 5 patients who presented with distal vaginal
atresia who were recruited between 2017 and 2018. Whole-exome sequencing was performed
in each subject with distal vaginal atresia. Sanger sequencing was used to confirm
the potential causative genetic mutation.
Setting
Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
Participants and Main Outcome Measures
The main outcome measure was the rare mutations potentially associated with distal
vaginal atresia in 5 patients.
Results
A truncating mutation c.266delC (p.P89Rfs*5) in the T-box transcription factor 6 (TBX6) gene, which is highly expressed in the human vagina, was identified in 1 patient
using whole-exome sequencing. The deletion of the 16p11.2 region containing the TBX6 locus has also been reported previously to have the clinical feature of Müllerian
agenesis. This mutation was paternally inherited by the patient. This truncating mutation
was absent from all of the databases we checked, suggesting that the variant is rare
and pathogenic.
Conclusion
We showed, to our knowledge, for the first time, that the mutation in TBX6 might be associated with human distal vaginal atresia.
Key Words
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References
- The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review.Hum Reprod Update. 2011; 17: 761
- Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal.Hum Reprod Update. 2008; 14: 415
- The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies.Hum Reprod. 2013; 28: 2032
- Pitfalls in diagnosis and management of distal vaginal agenesis: 10-year experience at a single centre.Eur J Obstet Gynecol Reprod Biol. 2012; 163: 85
- Surgical correction of vaginal anomalies.Clin Obstet Gynecol. 2008; 51: 223
- Congenital absence of the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome.Ann Intern Med. 1976; 85: 224
- Mayer-Rokitansky-Kuster-Hauser syndrome presenting as vaginal atresia: report of two cases.G Chir. 2008; 29: 165
- Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for clinical diagnosis and staging.Hum Reprod. 2006; 21: 792
- Genetics of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome.Clin Genet. 2017; 91: 233
- Copy number variation and regions of homozygosity analysis in patients with MULLERIAN aplasia.Mol Cytogenet. 2018; 11: 13
- Mutations in WNT9B are associated with Mayer-Rokitansky-Kuster-Hauser syndrome.Clin Genet. 2016; 89: 590
- TBX6, LHX1 and copy number variations in the complex genetics of Müllerian aplasia.Orphanet J Rare Dis. 2013; 8: 125
- Variations in RBM8A and TBX6 are associated with disorders of the mullerian ducts.Fertil Steril. 2015; 103: 1313
- Frame shift mutation of LHX1 is associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome.Hum Reprod. 2012; 27: 2872
- High incidence of distal vaginal atresia in mice lacking Tyro3 RTK subfamily.Mol Reprod Dev. 2008; 75: 1775
- Identification of the first homozygous POLG mutation causing non-syndromic ovarian dysfunction.Climacteric. 2018; 21: 467
- Observations on the Development of the Human Female Genital Tract.Carnegie Institution of Washington, Washington1930
- Mitotic rate and autoradiographic studies on the derivation and differentiation of the epithelium in the mouse vaginal anlage.Acta Anat (Basel). 1965; 62: 266
- The development of the human vagina.J Anat. 1957; 91: 490
- The association of uterine and renal anomalies.Obstet Gynecol. 1978; 51: 559
- Embryological observations on the female genital tract.Hum Reprod. 1992; 7: 437
- Experimental contributions to the study of the embryology of the vagina.Hum Reprod. 2006; 21: 1623
- High incidence of recurrent copy number variants in patients with isolated and syndromic Müllerian aplasia.J Med Genet. 2011; 48: 197
- TBX6 null variants and a common hypomorphic allele in congenital scoliosis.N Engl J Med. 2015; 372: 341
- Compound heterozygosity for null mutations and a common hypomorphic risk haplotype in TBX6 causes congenital scoliosis.Hum Mutat. 2017; 38: 317
- Autosomal recessive variations of TBX6, from congenital scoliosis to spondylocostal dysostosis.Clin Genet. 2017; 91: 908
- Cell lineage of timed cohorts of Tbx6-expressing cells in wild-type and Tbx6 mutant embryos.Biol Open. 2017; 6: 1065
- Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6.Nature. 1998; 391: 695
- Tbx6, a mouse T-Box gene implicated in paraxial mesoderm formation at gastrulation.Dev Biol. 1996; 180: 534
- Tbx6 regulates left/right patterning in mouse embryos through effects on nodal cilia and perinodal signaling.PLoS One. 2008; 3: e2511
- Tbx6 controls left-right asymmetry through regulation of Gdf1.Biol Open. 2018; 7: bio032565
- Mouse vaginal opening is an apoptosis-dependent process which can be prevented by the overexpression of Bcl2.Dev Biol. 1997; 184: 115
- Critical role for Tbx6 in mesoderm specification in the mouse embryo.Mech Dev. 2003; 120: 837
- The chick somitogenesis oscillator is arrested before all paraxial mesoderm is segmented into somites.BMC Dev Biol. 2010; 10: 24
- Phagocytosis and clearance of apoptotic cells is mediated by MER.Nature. 2001; 411: 207
Article info
Publication history
Published online: June 21, 2019
Footnotes
The authors indicate no conflicts of interest.
Chunfang Chu and Lin Li contributed equally to this work.
Identification
Copyright
© 2019 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc.
