Study of Possible Genetic Factors Determining the Clinical Picture of Thalassemia Intermedia

Kaddah, N; Rizk, Samia; Kaddah, A. M.; Salama, Khaled N.; Lotfy, Hayam M.

doi:10.3923/jms.2009.151.155

Cited by 6 publications

(5 citation statements)

References 12 publications

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“…The patient's genotype distribution in our study was in agreement with Kaddah et al [22], Waye et al [23], Settin et al [24], and Jiffri et al 2010 [11] [25].…”

Section: Resultssupporting

confidence: 92%

Accuracy of Reverse Dot-Blot PCR in Detection of Different β-Globin Gene Mutations

EL-Fadaly

Abd-Elhameed

Abd-Elbar

et al. 2015

Indian J Hematol Blood Transfus

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Prevention programs for b-thalassemia based on molecular diagnosis of heterozygous carriers and/or patients require the use of reliable mutation screening methods. The aim of this study was to compare between direct DNA sequencing, and reverse dot-blot PCR in detection of different b-globin gene mutations in Egyptian children with b-thalassemia. Forty children with b-thalassemia were subjected to mutation analysis, performed by both direct DNA sequencing and b-globin , and cd39 C[T (2.5 %)'', While the genotypes of three patients (6 alleles 7.5 %) were not detected by reverse dot-blot PCR. Mutant alleles detected by direct DNA sequencing were the same as reverse dot-blot PCR method except it revealed the genotypes of 3 undetected patients (one patient was homozygous IVSI-110 G[A, and two patients were homozygous IVS I-1 G[A. Sensitivity of the reverse dot-blot PCR was 92.5 % when compared to direct DNA sequencing for detecting b-thalassemia mutations. Our results therefore suggest that, direct DNA sequencing may be preferred over reverse dot-blot PCR in critical diagnostic situations like genetic counseling for prenatal diagnosis.

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“…The patient's genotype distribution in our study was in agreement with Kaddah et al [22], Waye et al [23], Settin et al [24], and Jiffri et al 2010 [11] [25].…”

Section: Resultssupporting

confidence: 92%

Accuracy of Reverse Dot-Blot PCR in Detection of Different β-Globin Gene Mutations

EL-Fadaly

Abd-Elhameed

Abd-Elbar

et al. 2015

Indian J Hematol Blood Transfus

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“…This study was in accordance with Kaddah et al, 2009, 14 who reported that the most common seven genetic mutations of the β thalassemia evaluated in Egyptian studies were IVSI-6, IVSI-110, IVSII-1, IVSII-745, IVSI-1, −87 and codon 39. Also Settin et al, 2006 15 stated that three abundant mutations were found accounting for a total 71.25% of all mutations; these 3 mutations were IVS I-110 (G→A), IVS I-6 (T→C) and IVS I-1 (G→A) representing 37.5%,17.5% and 16.25% respectively.…”

Section: Discussionsupporting

confidence: 92%

Spectrum of Beta Globin Gene Mutations in Egyptian Children With Β- Thalassemia

El-Shanshory¹,

Hagag

2014

Mediterr J Hematol Infect Dis

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BackgroundThe molecular defects resulting in a β-thalassemia phenotype, in the Egyptian population, show a clear heterogenic mutations pattern. PCR-based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of β-thalassemia is necessary for carrier screening, genetic counseling, and to offer prenatal diagnosis.The aim of the workwas to evaluate the different β-globin gene mutations in two hundred β-thalassemic Egyptian children.Subjects and MethodsThis study was carried out on two hundred β-thalassemic Egyptian children covering most Egyptian Governorates including 158 (79%) children with thalassemia major (TM) and 42 (21%) children with thalassemia intermedia(TI). All patients were subjected to meticulous history taking, clinical examination, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of the β-globin gene to detect the frequency of different mutations.ResultsThe most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A) 24%, IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon “Cd”39(C> T) 4%, −87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (−AA), Cd29(−G), Cd5 (−CT), Cd6(−A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G> C), Cd 28 (−C), Cap+1(A>C), −88(C>A), all of these rare mutations were present in 1%. There was a considerable variation in phenotypic severity among patients resulting from the interaction of different β∘ and β+mutations. Furthermore, no genotype-phenotype association was found both among the cases with thalassemia major and the cases with thalassemia intermedia.ConclusionDirect DNA sequencing provides insights for the frequency of different mutations in patients with β-thalassemia including rare and/or unknown ones. The most common mutations in Egyptian children with beta thalassemia were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A)24%, IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%.

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“…In Iranians, Kosaryan et al 15 found that 76% of β-thalassemia patients had either (+/−) or (+/+) for Xmnl limiting enzyme polymorphism. A previous study by Kaddah et al 16 reported positivity for 158 Xmnl polymorphism only in 2 of 22 (9%) Egyptian thalassemia intermedia patients, a value which is not significantly higher than the 4% heterozygous positivity in our β-thalassemia patients. This finding coincides with the conclusion of Neishabury et al 17 that the frequency of positive Xmnl Gγ polymorphism did not show a statistically significant difference between thalassemia major and intermedia cases in an Iranian study.…”

Section: Discussioncontrasting

confidence: 57%

Prevalence of Xmnl Gγ polymorphism in Egyptian patients with β-thalassemia major

Tantawy

Andrawes

Ismaeil

et al. 2012

Annals of Saudi Medicine

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BACKGROUND AND OBJECTIVESβ-thalassemia results from a deficiency of β-globin chains leading to an excess in α globin chains resulting in hypochromic microcytic red cells, ineffective erythropoiesis and hemolytic anemia. It is a result of a decline of HbF synthesis during the first year of life. F-cell levels are influenced by a sequence variant (C → T) at position −158 upstream of the -globin gene, so the frequency of the Xmnl Gγ polymorphism in Egyptian patients with β-thalassemia major needed evaluation to decide on the value of HbF augmentation drugs in treating Egyptian β-thalessemia.DESIGN AND SETTINGA cross-sectional study including 30 β-thalassemia major patients diagnosed and attending the Pediatric Hematology Unit, Children’s University Hospital, Ain Shams University, Cairo, Egypt, in the period from October 2008 to October 2009.PATIENTS AND METHODSThe 17 males and 13 females underwent a medical history and physical examination. Tests included a complete blood count, hemoglobin electrophoresis, serum ferritin, and detection of Xmnl Gγ polymorphism by PCR.RESULTSThe mean (SD) age was [2]10.2 (6.9) years. The most frequent genotype observed was homozygosity for the absence of the site XmnI (−/−) in 96% of cases. Heterozygosity (+/−) genotype was detected in 4% of cases, while homozygosity for the site XmnI (+/+) genotype was absent. Genotype was not related to age at first transfusion, fetal hemoglobin level or transfusion frequency.CONCLUSIONDespite the small sample size, the study demonstrated that Egyptian β-thalessemia patients have low frequency of positivity for the XmnI polymorphism whether in heterozygous (+/−) or homozygous (+/+) state.

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Study of Possible Genetic Factors Determining the Clinical Picture of Thalassemia Intermedia

Cited by 6 publications

References 12 publications

Accuracy of Reverse Dot-Blot PCR in Detection of Different β-Globin Gene Mutations

Accuracy of Reverse Dot-Blot PCR in Detection of Different β-Globin Gene Mutations

Spectrum of Beta Globin Gene Mutations in Egyptian Children With Β- Thalassemia

Prevalence of Xmnl Gγ polymorphism in Egyptian patients with β-thalassemia major

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