# Single gene pathogenic variants associated with BEEC (Bladder Exstrophy, Epispadias, Complex)

> **NIH NIH K23** · JOHNS HOPKINS UNIVERSITY · 2020 · $199,260

## Abstract

PROJECT SUMMARY
This K23 application is submitted by Angie C. Jelin, MD, Assistant Professor of Gynecology and
Obstetrics/Genetics at the Johns Hopkins School of Medicine. Dr. Jelin’s long term goal is to
become an independent investigator in fetal urinary tract anomalies. Towards this goal, she
proposes a mentored career development plan that provides training in whole genome
sequencing (WGS), genomics, CRISPR/Cas9, and mouse phenotyping.
Urogenital anomalies account for 20-30% of prenatally detected structural defects. Bladder
Exstrophy Epispadias Complex (BEEC) describes a subset of anomalies with a spectrum of
developmental defects ranging from a mild form of epispadias, to classic bladder exstrophy, to
omphalocele, exstrophy, imperforate anus, spinal anomalies (OEIS) complex. Patients with
BEEC suffer substantial morbidity and mortality due to impaired genito-urinary dysfunction. The
etiology of BEEC is largely unknown. Elucidating the underlying genetic component is critical to
gaining a better understanding of the developmental signaling pathways and is likely the first
step to developing targeted therapy. Variants in genes identified in other urogenital anomalies
appear to be responsible for some cases of BEEC including IS, WNT3, WNT9b, PLAG1 and
p63. We propose to take advantage of our extensive analytical experience in the Baylor
Hopkins Center for Mendelian Genomics and perform WGS on parent-proband trios for whom
the proband has BEEC. One study utilizing whole exome sequencing (WES), identified
candidate genes (SLC20A1 and CELSR3) in 2 out of 8 affected patients, providing reassurance
that our proposed strategy will be successful. Following WGS, we will explore the pathogenicity
of genetic variants by employing a knockout mouse model using CRISPR/Cas9 technology via
collaboration with the Jackson Laboratory. Final validation will include mouse phenotyping by
dynamic contrast-enhanced MRI under the expertise of, Cory Brayton, mouse pathologist.
Aim 1. To identify the genetic basis of BEEC through Whole Genome Sequencing (WGS)
Aim 2a. To create the founder (F0) homozygous knockout mouse using CRISPR/Cas9.
Aim 2b. To define the murine model phenotype using dynamic contrast enhanced MRI.

## Key facts

- **NIH application ID:** 9928453
- **Project number:** 5K23DK119949-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Angie Child Jelin
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,260
- **Award type:** 5
- **Project period:** 2019-05-10 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928453

## Citation

> US National Institutes of Health, RePORTER application 9928453, Single gene pathogenic variants associated with BEEC (Bladder Exstrophy, Epispadias, Complex) (5K23DK119949-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9928453. Licensed CC0.

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