Clinical trial NCT06433570: Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients
Official title: Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: EKLF Mutations in Beta Thalassemia Patients
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2024-05-29
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: cross sectional study

Brief summary: * 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Detection of KLF1 gene mutations in patients with beta thalassemia considering the beta molecular status of these patients
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Reem Abd Elkhalek Mohamed, lecturer
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Hebatallah Ahmed, lecturer
role: STUDY_DIRECTOR
References:
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