Clinical trial NCT05133388: The Prevelence of HBB c.93-21 G-A in β Thalassemia Patients
Official title: The Prevelence of HBB c.93-21 G-A Gene Mutation in Suspected Cases of β Thalassemia in Assiut University Hospitals.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Beta-Thalassemia
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2021-11-24
Enrollment: 150
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Assiut University Hospitals patients

Brief summary: * To design an amplification-refractory mutation system (ARMS) for the DNA diagnosis of the IVS I-110 (G\>A) \[HBB:c.93-21G˃A\] mutation.
* To detect the prevelence of the mutation among Assiut University Hospital patients.
* Phenotype/genotype correlation of the mutation.

Detailed description: * The β-thalassaemias result from over 300 gene mutations (Kurtoğlu A,et al 2016)
* These mutations are regionally specific and the spectrum of mutations has been determined for most at-risk populations. The strategy for identifying β-thalassaemia mutations is usually based on knowledge of the common mutations in the ethnic group of the individual being screened (Old JM, 2007).

The β globin gene mutation \[HBB:c.93-21G˃A\] or IVS I-110 (G\>A) is the most common β globin gene mutation in the Mediterranean region (Old JM, 2007). . There is no consensus about the % of the mutation among β thalassemic patients in Egypt \[has been reported (25.8%) by El-Gawhary et al. 2007, (33.75%) by Soliman et al. 2010, (48%) by El-Shanshory et al. 2014, (22%) by Elmezayen et al. 2015 and (34%) by Elhalfawy et al. 2017\].

According to the HbVar site, it represents 33% of the β globin gene mutations in the Egyptians. 28.5% according to Henderson S ,et al 2009 .

* The mechanism of this mutation depends on formation of a new splicing site resulting in 80% abnormal spliced mRNA and 20% normal mRNA .
* The molecular characterization of the globin gene mutation is necessary for definite diagnosis, genetic counseling, and in prenatal diagnosis.
* The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base changes or small deletions.
* The DNA is analyzed after amplification by PCR for Detection of point mutation IVS I-110 (G\>A) by Using primer pairs that only amplify individual alleles.

Eligibility criteria: Inclusion Criteria:

* β thalassemia (suspected \& clinically diagnosed cases)

Exclusion Criteria:

* Iron deficiency anaemia, anaemia of chronic disease, types of haemolytic anaemias other than thalassemia, other types of thalassemia and Hb variants.

Primary outcomes:
measure: Introduction of arms pcr in diagnosis .
timeFrame: 2 years
measure: Database initation .
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Faculty of Medicine Assiut University
Study officials:
affiliation: Assiut University
name: Ola Afifi
role: STUDY_DIRECTOR
References:
citation: Henderson S, Timbs A, McCarthy J, Gallienne A, Van Mourik M, Masters G, May A, Khalil MS, Schuh A, Old J. Incidence of haemoglobinopathies in various populations - the impact of immigration. Clin Biochem. 2009 Dec;42(18):1745-56. doi: 10.1016/j.clinbiochem.2009.05.012. Epub 2009 Jun 1.
citation: Old JM. Screening and genetic diagnosis of haemoglobinopathies. Scand J Clin Lab Invest. 2007;67(1):71-86. doi: 10.1080/00365510601046466.
citation: El-Gawhary S, El-Shafie S, Niazi M, Aziz M, El-Beshlawy A. Study of beta-Thalassemia mutations using the polymerase chain reaction-amplification refractory mutation system and direct DNA sequencing techniques in a group of Egyptian Thalassemia patients. Hemoglobin. 2007;31(1):63-9. doi: 10.1080/03630260601057104.
citation: Soliman OE, Yahia S, Shouma A, Shafiek HK, Fouda AE, Azzam H, Abousamra NK, Mahfouz R, Goda EF, El-Sharawy SA. Reverse hybridization StripAssay detection of beta-thalassemia mutations in northeast Egypt. Hematology. 2010 Jun;15(3):182-6. doi: 10.1179/102453310X12583347010214.
citation: El-Shanshory M, Hagag A, Shebl S, Badria I, Abd Elhameed A, Abd El-Bar E, Al-Tonbary Y, Mansour A, Hassab H, Hamdy M, Alfy M, Sherief L, Sharaf E. Spectrum of Beta Globin Gene Mutations in Egyptian Children with beta-Thalassemia. Mediterr J Hematol Infect Dis. 2014 Nov 1;6(1):e2014071. doi: 10.4084/MJHID.2014.071. eCollection 2014.
citation: Elmezayen AD, Kotb SM, Sadek NA, Abdalla EM. beta-Globin Mutations in Egyptian Patients With beta-Thalassemia. Lab Med. 2015 Winter;46(1):8-13. doi: 10.1309/LM1AYKG6VE8MLPHG.
citation: Kurtoglu A, Karakus V, Erkal O, Kurtoglu E. beta-Thalassemia gene mutations in Antalya, Turkey: results from a single centre study. Hemoglobin. 2016 Nov;40(6):392-395. doi: 10.1080/03630269.2016.1256818. Epub 2017 Mar 3.