# Exome Sequencing in Disorders of Sex Development: Impact on Patients and Families

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $177,000

## Abstract

Project Summary/Abstract
Genetic testing is an integral part of the evaluation of patients with disorders of sex development (DSD), and
the arrival of whole-exome sequencing in the clinic has the potential to greatly facilitate the diagnosis of DSD.
However, several barriers prevent this approach from reaching its full clinical potential. Our incomplete
knowledge of both the genes and the specific variants associated with DSD impairs our ability to recognize
pathogenic mutations. Despite growing evidence that mutations in DSD genes can produce a broad spectrum
of phenotypes, current guidelines recommend restricting the evaluation for DSD to severe cases of
undervirilization or overvirilization, resulting in potential missed opportunities both for diagnosis and for
understanding the full range of genotype-phenotype associations for DSD genes. Psychosocial outcomes of
genetic testing have been understudied in patients and families affected by DSD, and while whole-exome
sequencing has the potential to provide valuable diagnostic information, it may not produce a clear diagnosis in
many cases and has the potential to add to anxiety and stress.
This project will address these barriers by applying and evaluating whole-exome sequencing in subjects with
DSD and related conditions. Aim 1 of this project uses whole-exome sequencing both in patients with
“textbook” presentations of DSD as well as in patients with an expanded spectrum of presentations of apparent
undervirilization (such as hypospadias with or without bifid scrotum) or apparent overvirilization (such as
isolated clitoromegaly). Aim 2 of this project assesses the impact of returning genetic testing results on parents
using a series of validated measures, including assessments of anxiety, stress, expectations, and utility.
These studies will provide essential information to direct the use of whole-exome sequencing in the clinical
care of patients with broad range of conditions that result in apparent over/undervirilization.

## Key facts

- **NIH application ID:** 9988465
- **Project number:** 5R01HD089521-05
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Yee-Ming Chan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,000
- **Award type:** 5
- **Project period:** 2016-09-10 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988465

## Citation

> US National Institutes of Health, RePORTER application 9988465, Exome Sequencing in Disorders of Sex Development: Impact on Patients and Families (5R01HD089521-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9988465. Licensed CC0.

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