Mutations and Phenotypes of Unclassifiable Inherited Bone Marrow Failure Syndromes

Identification of The Novel Mutations and A Comprehensive Analysis of The Phenotype and Genetic Etiology Underlying Unclassifiable Inherited Bone Marrow Failure Syndromes With Bone Fragility Fractures

Inherited bone marrow failure syndromes (IBMFSs) are a diverse collection of genetic illnesses characterized by various degrees of peripheral cytopenias due to defective single-lineage or multi-lineage hematopoiesis, it can manifest itself at birth or later in life.

Study Overview

• Status: Recruiting
• Conditions: Inherited BMF Syndrome
• Intervention / Treatment: Genetic: The whole-exome sequencing

Detailed Description

Studying the genetic etiology underlying unclassifiable IBMFSs with bone fragility fractures should be useful for clarifying the undiagnosed pathophysiological mechanisms and other accessory factors to improve the diagnosis, follow-up, prognosis, and management of these patients as well as prevent future complications.

Moreover, early diagnosis of risk factors of unusual presentations of IBMFSs will be a useful tool for better treatment strategy.

In addition, along with typical IBMFSs, novel clinical entities must be included in an overall molecular portrait of IBMF disorders. As a result, comprehensive genetic analysis will be effective in establishing an accurate genetic diagnosis at medical evaluation.

• Study Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

• Study Contact: Name: Mahmoud I Elbadry, PhD; Phone Number: +201065964083; Email: mahmoudibrahem837@gmail.com

Study Locations

• Egypt
  • Sohag, Egypt, 82524
    • Recruiting
    • , Faculty of Medicine, Sohag University
    • Contact: Mahmoud I. Elbadry, MD, PhD; Phone Number: +01065964083; Email: mahmoudibrahim@med.sohag.edu.eg

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The candidate patients who will have evidence of unclassifiable IBMFSs and/or will present with manifestations suggesting IBMFSs and agree to comply with follow-up instructions will be screened for enrollment in this study.

Description

Inclusion Criteria:

• Confirmed a two-generational family with IBMFSs presented with signs and symptoms of bone fragility fractures and admitted or treated in Hematology Division at Internal Medicine Departments of various university hospitals will be screened for enrollment in this study.
• The investigators will invite the entire family for testing for IBMFSs mutations, and three additional family members consented to participate in this study.

Exclusion Criteria:

• • Patients will be diagnosed with paroxysmal nocturnal hemoglobinuria

  • Patients will be diagnosed with de novo myelodysplastic syndrome
  • IBMFSs-patients will refuse to consent to this study.
  • Serologic evidence of recent virus infection as hepatitis A (HAV), HBV, HCV, HEV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), or positive test for HIV.
  • IBMFSs patients with severe systemic diseases (such as cardiovascular, renal, and hepatic disease) or surgical/medical conditions that might interfere with follow-up instructions.
  • IBMFs patients with psychiatric disorders or a history of drug abuse,

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Progression of pancytopenia	Progression of pancytopenia severity	Two year after diagnosis
Number of Participants with Fragility Fractures	occurrence of the Fragility Fractures	Two year after diagnosis
Number of Participants with Malignancy transformation	Occurrence of hematological or solid malignancy	Two year after diagnosis

Collaborators and Investigators

• Sponsor: Sohag University
• Collaborators: Assiut University; Kyoto University
• Investigators: Principal Investigator: Mahmoud I Yousef, PhD, Faculty of Medicine, Sohag University

Publications and helpful links

General Publications

• Sieff CA. Acquired and Inherited Bone Marrow Failure Syndromes. Hematol Oncol Clin North Am. 2018 Aug;32(4):xiii-xiv. doi: 10.1016/j.hoc.2018.05.001. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2028

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 23, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Bone Marrow Diseases; Hematologic Diseases; Infant, Newborn, Diseases; Syndrome; Bone Marrow Failure Disorders; Pancytopenia; Congenital Bone Marrow Failure Syndromes
• Other Study ID Numbers: Soh-Med-22-01-40

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