# The Genetics and penetrance of the Mullerian Anomalies: Addressing the Challenges of the bench to bedside gap.

> **NIH NIH R03** · YALE UNIVERSITY · 2023 · $240,253

## Abstract

PROJECT SUMMARY:
The proposed collaboration will develop a multi-pronged research program by combining the expertise of
multiple collaborators to address the genetic causes of Müllerian anomalies (MAs). MAs are a relatively
common developmental abnormality of the Müllerian ducts in females, leading to atypical variations of the
uterine and vaginal anatomy. MAs are complex gynecological birth defects occurring in 5.5% of the general
female population, 8% of infertile women, 13% of women with miscarriages and 24.5% of those with
miscarriages and infertility. Despite the immense impact on woman’s health, the etiology of MAs remains
largely unknown. Although familial inheritance of MAs has been described, no single gene or mutation has
been found to be responsible for MAs. Understanding the heritability and broader health implications of
MAs is desperately needed. This multidisciplinary collaboration provides a unique opportunity to examine
population phenotypes, genetic factors, and molecular mechanisms involved in MAs to bridge clinical and
basic science research on this birth defect. In focusing on these complementary inquiries, this research will
bring together a multidisciplinary team to address significant gaps in our knowledge of this disease.
Further, our team of experts in pediatric gynecology, genomics, developmental biology, and modern data
science will formulate collaborative experimental approaches to collect invaluable preliminary data to
support a future R01 application. The research will address three key gaps in MA studies: (1) analysis of
the phenotypic spectrum and prevalence of MAs diagnoses (including population frequencies and
phenotypic clusters) via the use of the Cerner Real-World Dataset (2) identification of candidate gene
variants potentially causing disruption of reproductive tract development and MAs via genetic testing of
patients with MAs and their unaffected family members using whole exome sequencing (WES) , and (3)
systematic functional testing of selected candidate genes in the pathogenesis of MAs via in vivo functional
genomic analyses. The successful accomplishment of the Aims by this team will address several
recognized short-term and long-term research goals of critical clinical translational value.

## Key facts

- **NIH application ID:** 10668122
- **Project number:** 1R03HD109641-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Mustafa K Khokha
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $240,253
- **Award type:** 1
- **Project period:** 2023-08-29 → 2025-08-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10668122

## Citation

> US National Institutes of Health, RePORTER application 10668122, The Genetics and penetrance of the Mullerian Anomalies: Addressing the Challenges of the bench to bedside gap. (1R03HD109641-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10668122. Licensed CC0.

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