Longitudinal Studies of Patient With FPDMM

Sponsor

National Human Genome Research Institute (NHGRI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT03854318

Collaborator

(none)

1,000

Enrollment

Location

117.2

Anticipated Duration (Months)

8.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

Genes tell the body and its cells how to work. Familial platelet disease (FPD) or FPD with associated malignancies (FPDMM) is caused by a mutation in the gene RUNX1. People with this disease may have problems with their blood and bleed for a long time when they are injured. Researchers want to learn more about RUNX1 mutations and FPD.

Objective:

To learn more about FPD in people with RUNX1 mutations to lead to better diagnosis, monitoring, and treatment.

Eligibility:

People any age with a suspected or confirmed RUNX1 mutation

People who have a family member with the mutation

Design:

All participants will be screened with a phone call and a blood, saliva, or cheek cell sample.

Participants with a suspected or confirmed mutation will have 1 visit. It will last about 2 days. They will then have visits at least once a year.

Visits will include:

Medical history and physical exam
Blood tests or saliva sample
Possible skin biopsy: A small piece of the participant s skin will be removed.
Bone marrow aspiration or biopsy: The participant s bone marrow will be removed by needle from a large bone such as the hip bone.
Possible apheresis: Blood will be removed from the body and certain blood cells will be taken out. The rest of the blood is returned to the body.

Between visits, participants with a suspected or confirmed mutation will keep a diary of disease symptoms and signs.

Samples from all participants may be used for genetic testing

Condition or Disease	Intervention/Treatment	Phase
Inherited Hematological Diseases Rare Diseases FPDMM

Detailed Description

Germline mutations in RUNX1 are responsible for familial platelet disorder with associated myeloid malignancies (FPDMM, or simply FPD), an autosomal dominant disease characterized by defective megakaryocytic development, low platelet counts, prolonged bleeding times, and a life-long risk of developing hematological malignancies. Disease penetrance and clinical presentations vary among families with different germline RUNX1 mutations, and even among affected individuals within a single family. Currently there are no biomarkers or assays to predict which patients will progress to malignancy, and some patients present with acute myeloid leukemia (AML) as their initial manifestation of the germline syndrome. We propose to characterize the etiology and natural history of patients with FPDMM and RUNX1 mutations, both known and yet-to-be discovered. We will investigate those patients and families with FPDMM-like

diseases but without RUNX1 mutations, to understand the genetic basis for their diseases. In so doing, we will expand our knowledge about this disorder and provide access to patients of interest for research, teaching, and clinical experience. The knowledge gained

through this study will lead to better understanding of the disease progression, both clinically and at molecular levels, which may result in the development of better diagnosis, monitoring, and innovative therapies.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Longitudinal Studies of Patients With FPDMM

Actual Study Start Date :

Mar 28, 2019

Anticipated Primary Completion Date :

Dec 31, 2028

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Family Direct family members of enrolled patients will be asked to enroll in the study to provide specimens for genetic testing, next-generation sequencing, and other related studies.
RUNX1 Patients enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation.

Outcome Measures

Primary Outcome Measures

Natural History [Ongoing]
This protocol continues the decades-long tradition of identifying and examining patients with rare genetic diseases and characterizing the natural history.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITIERIA:
Patients enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation.
Unaffected family members may be asked to enroll in the study to provide specimens (blood, skin) for genetic testing, next-generation sequencing, and other related studies.
Enrolled subjects can be either sex and any age. There are no upper or lower age restrictions on this study.