## Protocol Section
### Identification Module
**NCT ID:** NCT06433570

**Brief Title:** 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

#### Organization Study ID Info
**ID:** EKLFmutation in β thalassemia
#### Organization
**Class:** OTHER
**Full Name:** Assiut University
### Status Module
#### Completion Date
**Date:** 2027-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-23
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Assiut University

#### Responsible Party

**Investigator Affiliation:** Assiut University

**Investigator Full Name:** Mohamed Abd Elnasser Mahmoud

**Investigator Title:** Assiut

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- EKLF Mutations in Beta Thalassemia Patients

### Design Module

#### Design Info

**Observational Model:** CASE_ONLY

**Time Perspective:** CROSS_SECTIONAL

#### Enrollment Info

**Count:** 100

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Genetic: multiplex PCR

**Label:** 50 patients with beta thalassemia intermedia

#### Arm Group 2

**Intervention Names:**

- Genetic: multiplex PCR

**Label:** 50 patients with beta thalassemia major

### Interventions

#### Intervention 1

**Arm Group Labels:**

- 50 patients with beta thalassemia intermedia

- 50 patients with beta thalassemia major

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

**Name:** multiplex PCR

**Type:** GENETIC

### Outcomes Module

#### Primary Outcomes

**Description:** 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 and with the clinical data (frequency of blood transfusions).

**Measure:** Detection of KLF1 gene mutations in patients with beta thalassemia considering the beta molecular status of these patients

**Time Frame:** Baseline

### Eligibility Module

**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

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

**Study Population:** cross sectional study

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** doctor4egypt2011@yahoo.com

**Name:** mohamed mahmoud

**Phone:** 01113225644

**Role:** CONTACT

**Contact 2:**

**Email:** Somaia2020m@gmail.com

**Name:** Somia Mohammed, prof

**Phone:** 01118279876

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Assiut University

**Name:** Reem Abd Elkhalek Mohamed, lecturer

**Role:** STUDY_DIRECTOR

**Official 2:**

**Affiliation:** Assiut University

**Name:** Hebatallah Ahmed, lecturer

**Role:** STUDY_DIRECTOR

### References Module

#### References

**Citation:** 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.

**PMID:** 21613252

**Citation:** 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.

**PMID:** 23474875

**Citation:** 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.

**PMID:** 35667093

**Citation:** 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.

**PMID:** 20676099

**Citation:** 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.

**PMID:** 35154532

**Citation:** 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.

**PMID:** 25976964

**Citation:** 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.

**PMID:** 30529538

**Citation:** 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.

**PMID:** 31111750

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

**PMID:** 20001619

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

**PMID:** 27811859

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000000745

- Term: Anemia, Hemolytic, Congenital

- ID: D000000743

- Term: Anemia, Hemolytic

- ID: D000000740

- Term: Anemia

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000006453

- Term: Hemoglobinopathies

- ID: D000030342

- Term: Genetic Diseases, Inborn

### Condition Browse Module - Browse Branches

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16557

- Name: Thalassemia

- Relevance: HIGH

- As Found: Thalassemia

- ID: M19408

- Name: beta-Thalassemia

- Relevance: HIGH

- As Found: Beta Thalassemia

- ID: M4070

- Name: Anemia

- Relevance: LOW

- As Found: Unknown

- ID: M9547

- Name: Hemolysis

- Relevance: LOW

- As Found: Unknown

- ID: M4073

- Name: Anemia, Hemolytic

- Relevance: LOW

- As Found: Unknown

- ID: M4075

- Name: Anemia, Hemolytic, Congenital

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9539

- Name: Hemoglobinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: T5622

- Name: Thalassemia

- Relevance: HIGH

- As Found: Thalassemia

- ID: T737

- Name: Beta-thalassemia

- Relevance: HIGH

- As Found: Beta Thalassemia

### Condition Browse Module - Meshes

- ID: D000013789

- Term: Thalassemia

- ID: D000017086

- Term: beta-Thalassemia

### Misc Info Module

- Version Holder: 2024-05-31
