Ovarian Function and Gynecological Profile of Patients Carrying a Pathogenic Variant of the HNF1B Gene (GYN-HNF1) (GYN-HNF1)

Study of Ovarian Function and Gynecological Profile of Patients Carrying a Pathogenic Variant of the HNF1B Gene (GYN-HNF1)

The main objective of this study is to study the ovarian function of patients with hepatocyte nuclear factor-1beta (HNF1B) abnormality, followed in the reference centers of Toulouse and Paris University Hospitals. The secondary objectives are to know the gynecological profile of these patients.

A dosage of anti-mullerian hormone (AMH) will be added to the usual balance, whatever the phase of the cycle and a pelvic ultrasound will be performed by the same operator by center. Patients will be received in a dedicated consultation to complete a questionnaire on gynecological and obstetric history, as well as their personal and family history. There will be no gynecological examination during this consultation.

Study Overview

• Status: Completed
• Conditions: Genital Diseases, Female
• Intervention / Treatment: Other: Pelvic ultrasound; Biological: blood sample

Detailed Description

HNF1B mutations can be responsible for genital malformations associated with renal development abnormalities. HNF1b is also a candidate gene involved in the development of the renal tract and the Mullerian system but there is no data in the literature regarding the ovarian function and clinical gynecological profile of these patients.

The main objective of this study is to study the ovarian function of patients with HNF1B abnormality, followed in the reference centers of Toulouse and Paris University Hospitals. The secondary objectives are to know the gynecological profile of these patients.

A dosage of AMH will be added to the usual balance, whatever the phase of the cycle and a pelvic ultrasound will be performed. Patients will be received in a dedicated consultation to complete a questionnaire on gynecological and obstetric history, as well as their personal and family history. There will be no gynecological examination during this consultation.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catherine PIENKOWSKI, MD; Phone Number: 33 05 34 55 85 53; Email: pienkowski.c@chu-toulouse.fr

Study Locations

• France
  • Paris, France, 75743
    • Necker Hospital
    • Contact: Sabrina Da costa, Dr; Email: sabrina.dacosta@aphp.fr
    • Principal Investigator: Sabrina Da costa, MD
    • Sub-Investigator: Alaa Cheikhelard, MD
  • Paris, France, 75651
    • Pitié Salpêtrière Hospital -
    • Contact: Zeina Chakhtoura, MD; Phone Number: +33 01 42 16 02 20; Email: zeina.chakhtoura@psl.aphp.fr
    • Principal Investigator: Zeina Chakhtoura, Pr
  • Toulouse, France, 31059
    • Toulouse University Hospital
    • Contact: Catherine PIENKOWSKI, MD; Phone Number: +33 5 34 55 85 53; Email: pienkowski.c@chu-toulouse.fr
    • Principal Investigator: Catherine PIENKOWSKI, MD
    • Sub-Investigator: Audrey Cartault, MD
    • Sub-Investigator: Perrine Ernoult, MD
    • Sub-Investigator: Stéphane Decramer, PH
    • Sub-Investigator: Dominique Chauveau, PH
    • Sub-Investigator: Stanislas Faguer, PH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Girls from 12 years of age carrying a pathogenic variant of the HNF1 B gene and monitored in the reference center for rare renal diseases
• Person affiliated or beneficiary of a social security scheme.
• Free, informed and written consent signed by the participant or her legal representative if a minor patient and the investigator (at the latest on the day of inclusion and before any examination required by the research).

Exclusion Criteria:

• Woman unable to answer
• Pregnant or breastfeeding woman
• Refusal of participation by the patient or her legal representative
• Person under a protection system for adults (such as safeguard of justice, guardianship or curatorship)
• History of chemotherapy, radiotherapy, brachytherapy
• History of ovarian endometrium

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: patient with a mutation in the HNF1B gene; Patient with a mutation in the HNF1B gene and which are followed in the reference centers	Other: Pelvic ultrasound; Pelvic or vaginal ultrasound; Biological: blood sample; blood sample (5ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum level of Antimullerian Hormone levels	serum level of antimullerian hormone levels in ng/mL	day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ultrasound result	ultrasound (pelvic or vaginal) will allow the team to look at whether or not there is a genital defect and the type of defect.	day 1

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Catherine PIENKOWSKI, MD, University Hospital, Toulouse

Publications and helpful links

General Publications

• Edghill EL, Bingham C, Ellard S, Hattersley AT. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet. 2006 Jan;43(1):84-90. doi: 10.1136/jmg.2005.032854. Epub 2005 Jun 1.
• Lindner TH, Njolstad PR, Horikawa Y, Bostad L, Bell GI, Sovik O. A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta. Hum Mol Genet. 1999 Oct;8(11):2001-8. doi: 10.1093/hmg/8.11.2001.
• Oram RA, Edghill EL, Blackman J, Taylor MJ, Kay T, Flanagan SE, Ismail-Pratt I, Creighton SM, Ellard S, Hattersley AT, Bingham C. Mutations in the hepatocyte nuclear factor-1beta (HNF1B) gene are common with combined uterine and renal malformations but are not found with isolated uterine malformations. Am J Obstet Gynecol. 2010 Oct;203(4):364.e1-5. doi: 10.1016/j.ajog.2010.05.022. Epub 2010 Jul 15.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): October 12, 2023
• Study Completion (Actual): October 12, 2023

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: ovarian function; gene HNF1b mutation; genital malformations
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases, Female; Genital Diseases
• Other Study ID Numbers: RC31/20/0124; 2020-A02800-39 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No