Phenotypic and Genotypic Identification and Characterization of MYH9-related Constitutional Thrombocytopenia (MAGIC-MYH9)

The research involves the establishment of a cohort including as much as possible cases of macrothrombocytopenia related to a "MYH9 syndrome" and the study of mutations and polymorphisms of MYH9 gene in all these patients. As MYH9 syndrome is an autosomal dominant disorder, patients should be heterozygous for a MYH9 gene mutation.

The main goal of our project is looking for correlations between genotype and phenotype. It is planned to characterize the phenotype and genotype of a cohort of patients, including family members that will be addressed during the study in order to better understand the platelet disorder and improve the epidemiological knowledge of MYH9 syndrome. The data will be recorded in a database.

Study Overview

• Status: Completed
• Conditions: May-Hemalin; Fechtner Syndrome (Disorder); Epstein Syndrome (Disorder); MYH9 Related Disorders

Detailed Description

Definition: Extended description of the protocol, including information not already contained in other fields, such as comparison(s) studied. The patients that will participate in the study will be suffering or suspected suffering from MYH9 syndrome.

The study of MYH9 gene will be proposed to the patients but also to both parents of the propositi and other family members (children and adults), whether symptomatic or not. The relatives who will be proved to be heterozygotes for a MYH9 mutation will be considered as new cases and therefore included in the cohort of patients.

Four groups of controls (individuals who are not affected by a decrease in the platelet count) will be constituted:

A1: controls for proplatelets production study A2: controls for platelet proteome study B: controls for MYH9 gene analysis C: controls for leukocytes immunofluorescence study

Patients Patients will be included at the 6 sites of the national Reference Center for Inherited Platelet Disorders (CRPP) after signing an informed consent form. During the visit of inclusion (V1), data usually required for the diagnosis of MYH9 syndrome will be collected: clinical examination, auditory and ocular check, blood tests including MYH9 gene analysis, and search for proteinuria.

Among patients with a MYH9 mutation, a limited number will be recruited in a second step for participating to specific studies focused on the consequences of MYH9 mutations on the proplatelets production and the platelet proteome. The selected patients should be representative of the different phenotypes of MYH9 syndrome. They should be adults and have a platelet count above 50 G / L. A blood sample will be drawn for this purpose during a second visit (V2).

An annual control will be offered at year 1, year 2 and year 3 after inclusion to all the patients confirmed to have MYH9 syndrome (with MYH9 mutation). Each control will include: clinical examination and record of bleeding episodes, if any, during the past year, blood tests, search for proteinuria. The last control (end of the study) will also include auditory and ocular tests.

Relatives The relatives will be included in the study after signing informed consent form during an inclusion visit (VAP) at one of the 6 sites of CRPP. During the visit, a blood sample will be drawn for platelet and MYH9 gene study.

Controls The controls will be included in the study after signing informed consent at 6 sites of the CRPP. During their inclusion visit (VT), a blood sample will be drawn for platelet and MYH9 gene study.

• Study Type: Observational
• Enrollment (Actual): 360

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Hôpital Robert Debré

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

defined population

Description

Inclusion Criteria:

1. Thrombocytopenia with large/giant platelets (macrothrombocytopenia=MT)

2. and at least one of the following criteria:

   • chronicity of the MT or MT at least found at 2 successive examinations
   • Leukocyte inclusions in polymorphonuclear neutrophils
   • Juvenile sensorineural hearing loss
   • Nephritis
   • Presenile cataracts
   • Familial cases with bleeding disorder associated at least with one of the following symptoms: thrombocytopenia, nephritis, cataracts, deafness, leukocyte inclusions in polymorphonuclear neutrophils
3. Patient who has given his consent
4. Patient who has a social insurance -

Exclusion Criteria:

• Other proven constitutional macrothrombocytopenia

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Study of the correlations phenotype - MYH9 genotype of the patients	final time frame at the end of the study

Secondary Outcome Measures

Outcome Measure	Time Frame
- Describe the initial clinical symptoms and the long- term evolution of MYH9-related macrothrombocytopenia - Explore the consequences of MYH9 gene mutations on the proplatelets production - Study the effects of MYH9 gene mutations on the platelet	final time frame at the end of the study

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Nicole Schlegel, MD,PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: June 19, 2009
• First Submitted That Met QC Criteria: June 19, 2009
• First Posted (Estimate): June 22, 2009

Study Record Updates

• Last Update Posted (Estimate): July 29, 2015
• Last Update Submitted That Met QC Criteria: July 27, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: nephritis; MYH9 gene; macrothrombocytopenia; leukocyte inclusions; cataracts deafness; MYH9 Related Disorders
• Additional Relevant MeSH Terms: Pathologic Processes; Hematologic Diseases; Blood Platelet Disorders; Syndrome; Disease; Thrombocytopenia
• Other Study ID Numbers: P070110