Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients

NCT ID: NCT06433570

Last Updated: 2024-05-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-06-30

Study Completion Date

2027-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

* Detection of KLF1 gene mutations in patients with beta thalassemia considering the alpha and beta molecular status of these patients.
* Study the relation between genotypic mutational status of KLF1 mutation with the level of Hb F and Hb A2 in the patients of beta thalassemia.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Thalassemias are inherited abnormalities in globin chain synthesis of hemoglobin and one of the most common single gene disorders in the world.

β-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of haemoglobin. Three clinical and hematological conditions of increasing severity are recognized: the β-thalassemia trait, thalassemia intermedia and thalassemia major.

The Erythroid Kruppel-like factor (EKLF or KLF1) is a master regulator of terminal erythroid differentiation, controlling expression of many key pathways and structures including cell division, the cell membrane and cytoskeleton, heme and globin synthesis.

The KLF1 works as a key regulator of γ-globin to β-globin switch by up-regulation of PUM1 that binds to fetal γ globin mRNA impairing its stability and translation and by Bcl11a expression that represses γ-globin expression.

Previous studies reported that KLF1 mutations have been identified in a variety of erythroid conditions like hereditary persistence of fetal hemoglobin, Congenital dyserythropoietic anemia and borderline HbA2.

An Indian study on KLF1 gene variations found a marginal significance in the thalassemia intermedia group (14%) as against the thalassemia major group (2.0%).

Also, a case report on a Chinese family with twin brothers, both of whom had the same genotype of β0/β0, reported that KLF1 mutations have a role in modulating the phenotypic severity of β-thalassemia.

In our study, where there is high incidence of beta thalassemia in Egypt, we try to detect KLF1 mutations and its relation to clinical phenotype of these patients.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

EKLF Mutations in Beta Thalassemia Patients

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

50 patients with beta thalassemia intermedia

multiplex PCR

Intervention Type GENETIC

Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients using multiplex PCR

50 patients with beta thalassemia major

multiplex PCR

Intervention Type GENETIC

Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients using multiplex PCR

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

multiplex PCR

Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients using multiplex PCR

Intervention Type GENETIC

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients with β-thalassemia (intermedia and major) of both genders at any age

Exclusion Criteria

* Patients with any other type of haemolytic anaemias.
* Patients on Hydroxyurea therapy
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Assiut University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Mohamed Abd Elnasser Mahmoud

Assiut

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Reem Abd Elkhalek Mohamed, lecturer

Role: STUDY_DIRECTOR

Assiut University

Hebatallah Ahmed, lecturer

Role: STUDY_DIRECTOR

Assiut University

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

mohamed mahmoud

Role: CONTACT

01113225644

Somia Mohammed, prof

Role: CONTACT

01118279876

References

Explore related publications, articles, or registry entries linked to this study.

Siatecka M, Bieker JJ. The multifunctional role of EKLF/KLF1 during erythropoiesis. Blood. 2011 Aug 25;118(8):2044-54. doi: 10.1182/blood-2011-03-331371. Epub 2011 May 25.

Reference Type BACKGROUND
PMID: 21613252 (View on PubMed)

Tallack MR, Perkins AC. Three fingers on the switch: Kruppel-like factor 1 regulation of gamma-globin to beta-globin gene switching. Curr Opin Hematol. 2013 May;20(3):193-200. doi: 10.1097/MOH.0b013e32835f59ba.

Reference Type BACKGROUND
PMID: 23474875 (View on PubMed)

Elagooz R, Dhara AR, Gott RM, Adams SE, White RA, Ghosh A, Ganguly S, Man Y, Owusu-Ansah A, Mian OY, Gurkan UA, Komar AA, Ramamoorthy M, Gnanapragasam MN. PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin. Blood Adv. 2022 Dec 13;6(23):6016-6022. doi: 10.1182/bloodadvances.2021006730.

Reference Type BACKGROUND
PMID: 35667093 (View on PubMed)

Borg J, Papadopoulos P, Georgitsi M, Gutierrez L, Grech G, Fanis P, Phylactides M, Verkerk AJ, van der Spek PJ, Scerri CA, Cassar W, Galdies R, van Ijcken W, Ozgur Z, Gillemans N, Hou J, Bugeja M, Grosveld FG, von Lindern M, Felice AE, Patrinos GP, Philipsen S. Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet. 2010 Sep;42(9):801-5. doi: 10.1038/ng.630. Epub 2010 Aug 1.

Reference Type BACKGROUND
PMID: 20676099 (View on PubMed)

Srivorakun H, Thawinan W, Fucharoen G, Sanchaisuriya K, Fucharoen S. Thalassemia and erythroid transcription factor KLF1 mutations associated with borderline hemoglobin A2 in the Thai population. Arch Med Sci. 2020 Aug 11;18(1):112-120. doi: 10.5114/aoms.2020.93392. eCollection 2022.

Reference Type BACKGROUND
PMID: 35154532 (View on PubMed)

Waye JS, Eng B. Kruppel-like factor 1: hematologic phenotypes associated with KLF1 gene mutations. Int J Lab Hematol. 2015 May;37 Suppl 1:78-84. doi: 10.1111/ijlh.12356.

Reference Type BACKGROUND
PMID: 25976964 (View on PubMed)

Hariharan P, Colah R, Ghosh K, Nadkarni A. Differential role of Kruppel like factor 1 (KLF1) gene in red blood cell disorders. Genomics. 2019 Dec;111(6):1771-1776. doi: 10.1016/j.ygeno.2018.11.032. Epub 2018 Dec 5.

Reference Type BACKGROUND
PMID: 30529538 (View on PubMed)

Xie XM, Liu YN, Li J, Jiang F, Li DZ. A Kruppel-Like Factor 1 Gene Mutation Ameliorates the Severity of beta-Thalassemia: A Case Report. Hemoglobin. 2019 Mar;43(2):137-139. doi: 10.1080/03630269.2019.1607373. Epub 2019 May 21.

Reference Type BACKGROUND
PMID: 31111750 (View on PubMed)

El-Beshlawy A, Youssry I. Prevention of hemoglobinopathies in Egypt. Hemoglobin. 2009;33 Suppl 1:S14-20. doi: 10.3109/03630260903346395.

Reference Type BACKGROUND
PMID: 20001619 (View on PubMed)

Origa R. beta-Thalassemia. Genet Med. 2017 Jun;19(6):609-619. doi: 10.1038/gim.2016.173. Epub 2016 Nov 3.

Reference Type RESULT
PMID: 27811859 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

EKLFmutation in β thalassemia

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.