Hypospadias and Exome: Identification of New Genes for Familial Hypospadias

Hypospadias is the second most common malformation of the male genitalia and consists in a congenital hypoplasia of its ventral face. Hypospadias results from abnormal development of the penis that leaves the urethral meatus proximal to its normal glanular position. Meatus position may be located anywhere along the penile shaft, but more severe forms of hypospadias may have a urethral meatus located at the scrotum or perineum. Glandular and penile anterior represents approximately 70% of all the diagnosed cases.

The frequency of family reached depend on the severity of hypospadias. The number of children which have hypospadias mutation discovered by classical technique is low. Families are often the cause of the discovery of new genes involved in sexual differentiation because they allow comparison of genomes of related persons, and detect more easily mutations.

Study Overview

• Status: Completed
• Conditions: Hypospadias
• Intervention / Treatment: Genetic: Exome sequencing

Detailed Description

The aim of this protocol is to search for new genes involved in genital malformations such as hypospadias. Addressed to families with usual causes of these malformations excluded. The search for these mutations will be done by exome sequencing in families where several cases of hypospadias were identified.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Hopital Lapeyronie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hypospadiac patients with a familial history of hypospadias

Exclusion Criteria:

• Hypospadiac patients without a family history of hypospadias
• Hypospadiac patients with a family history of hypospadias where etiology is identified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Hypospadias; Familial hypospadias trios (patients + parents)	Genetic: Exome sequencing; Plain DNA sequencing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of new genetic variants	exome sequencing	1 day

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Nicolas Kalfa, MD, PhD, UH Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2014
• Primary Completion (Actual): November 12, 2015
• Study Completion (Actual): April 24, 2024

Study Registration Dates

• First Submitted: June 15, 2015
• First Submitted That Met QC Criteria: July 10, 2015
• First Posted (Estimated): July 13, 2015

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Hypospadias; exome sequencing; genital malformation
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Congenital Abnormalities; Urogenital Abnormalities; Penile Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypospadias; Investigative Techniques; Genetic Techniques; Sequence Analysis; Sequence Analysis, DNA; Whole Genome Sequencing; Exome Sequencing
• Other Study ID Numbers: 9477; 2014-A01425-42 (Other Identifier: ANSM)