Whole-exome sequencing in girls with anomalies of uterus and/or vagina reveals a spectrum of autosomal dominant disorders

Polina N. Tsabai; Zalina K. Batyrova; Irina S. Mukosey; Alexander A. Voskoboinikov; Zaira Kh. Kumykova; Anna I. Turchinets; Irina I. Kirillova; Elena V. Uvarova; Jekaterina Shubina; Dmitry Yu. Trofimov

doi:10.1530/endoabs.118.PO90

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Endocrine Abstracts (2026) 118 PO90 | DOI: 10.1530/endoabs.118.PO90

IDSD2026 Poster Abstracts Poster Abstracts (93 abstracts)

Whole-exome sequencing in girls with anomalies of uterus and/or vagina reveals a spectrum of autosomal dominant disorders

Polina N. Tsabai ¹ , Zalina K. Batyrova ² , Irina S. Mukosey ¹ , Alexander A. Voskoboinikov ¹ , Zaira Kh. Kumykova ² , Anna I. Turchinets ² , Irina I. Kirillova ¹ , Elena V. Uvarova ² , Jekaterina Shubina ¹ & Dmitry Yu. Trofimov ¹

Author affiliations

¹Institute of Reproductive Genetics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of Ministry of Health of Russian Federation, Moscow, Russia; ²Department of Children and Adolescent Gynecology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of Ministry of Health of Russian Federation, Moscow, Russia. Correspondence to: [email protected]

Background: Congenital malformations of the reproductive organs are characterized by a variety of anatomical variants that lead to functional disorders due to complete or partial organ obstruction, infertility and adverse reproductive outcomes. The etiology of congenital uterine and/or vaginal malformations remains a subject of debate; several studies present data on candidate genes. This study aimed to investigate the genetic basis of uterine malformations in Russian patients.

Methods: A retrospective study was conducted on 108 girls with congenital malformations of the reproductive organs. The cohort included 45 patients with aplasia of the uterus and vagina (Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: type 1 - 19 patients, type 2 - 26 patients), 38 patients with uterine duplication, and 25 patients with vaginal atresia. Whole-exome sequencing was performed on DNA isolated from peripheral blood (NovaSeq 6000 Illumina). The clinical significance of the identified variants was assessed according to the recommendations for the interpretation of data obtained by high-throughput sequencing methods.

Results: Genetic variants potentially explaining the development of uterine and/or vaginal malformations were found in 17/108 patients (15.7%). In the MRKH group, variants were identified in 12/45 patients (27%), including MRKH type 1 - in 1/19 (5%), and MRKH type 2 - in 11/26 (42%). In patients with uterine duplication, variants were found in 3/38 (8%); these patients had Herlyn-Werner-Wunderlich syndrome. In cases of vaginal atresia, variants were detected in 2/25 patients (8%). Of the 17 genetic variants found, 12 were copy number variations: microdeletions of chromosomes 2q14.3q21.2, 16p11.2, 17q12, 22q11.21, and a microduplication of chromosome 5p13.2. Chromosomal micro-rearrangements were mainly detected in MRKH type 2 (8 cases), as well as in vaginal aplasia (2 cases) and Herlyn-Werner-Wunderlich syndrome (2 cases). In 5 cases, single nucleotide variants were found in the GREB1L (2 cases), WNT4, FLT4, and POGZ genes. All identified genetic variants follow an autosomal dominant inheritance pattern, which could potentially lead to the transmission of the uterine malformation to the patients’ daughters.

Conclusions: Comprehensive genetic testing of patients with uterine and vaginal malformations is advisable to clarify the etiology and provide a prognosis for planning pregnancy with autologous oocytes.