Revisiting beta thalassemia intermedia: past, present, and future prospects

Salah, N. Ben; Bou‐Fakhredin, Rayan; Mellouli, Fethi; Taher, Alì

doi:10.1080/10245332.2017.1333246

Cited by 24 publications

(20 citation statements)

References 93 publications

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“…In five members of the family (I-1, II-1, II-2, II-3 and II-4), we observed the presence of an a-globin genes duplication encompassing the regulatory HS-40 region. Their hematological data were consistent with previous reports of families carrying one b 0 -thal allele along with an a-cluster duplication (Harteveld et al, 2008;4 de la Torre et al Ben-Salah et al, 2017;Clark et al, 2018;Theodoridou et al, 2018). It is known that co-inheritance of a deletions represents a benefit for b-thal patients; on the other hand, increased a-globin chains due to genes duplication in bthal patients leads to a more severe phenotype (Mettananda et al, 2015;Saleh-Gohari et al, 2015;Shang and Xu 2017).…”

Section: Discussionsupporting

confidence: 90%

“…The minor form corresponds to the simple heterozygote condition whereas the beta-thalassemia major type refers to the more severe disorder with transfusion dependency as a result of the inheritance of two b 0 alleles. b-thal intermedia comprises a wide range of clinical features and is mainly characterized by occasional blood transfusions; b-thal intermedia is observed in different molecular forms such as, two b-thal alleles (b 0 /b +/+ , b 0 /b 0 ), one b-thal allele and additional copies of a-globin genes (b 0 /b A ; aaa/aa, aaaa/aa, aaaa/aaa) or the presence of a single dominant b-thal allele (b D /b A ) (Origa et al, 2014;Ben-Salah et al, 2017, Clark et al, 2018.…”

Section: Introductionmentioning

confidence: 99%

“…The pathophysiology of this disease is the outcome of an imbalanced ratio of aand non-a-globin chains (excess of a-globin chains), and the severity depends on three different mechanisms. First, the type of b allele (b 0 , b + or b ++ ), correlated to the amount of residual b-globin chains (Mettananda et al, 2015;Ben-Salah et al, 2017;Shang and Xu 2017;Zhong et al, 2018). Second is the co-inheritance of alpha globin locus defect, either an alpha-thalassemia deletion (a-thal) which is often observed in b-thal patients, resulting as a positive modifier or, conversely, the presence of additional copies of HBA2 or HBA1 genes which causes a more severe form of b-thal (Ben-Salah et al, 2017;Theodoridou et al, 2018;Clark et al, 2018;Harteveld et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Three Mexican Families with β thalassemia intermedia with different molecular basis

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Fjp

et al. 2019

Genet. Mol. Biol.

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Beta thalassemia (b-thal) is a frequent monogenic disease, is clinically and molecularly heterogeneous. This study described molecular and laboratory findings for three Mexican patients with b-thal intermedia phenotype and their relatives. Three Mexican families were studied for presenting b-thal intermedia, ARMS-PCR and Gap-PCR were performed to screen for common mutations, Sanger sequencing for rare or new alleles, and MLPA for identifying deletions and or duplications. In all three families we observed, in heterozygote condition, the mutation c.118C > T (p.Gln39*) also known as codon 39(C > T) in the b globin gene (HBB) associated with a novel molecular defect: a new duplication of the alpha globin gene cluster, a new deletion that includes the loss of exon 3 of HBB and finally a novel mutation in the 3'UTR of HBB (HBB: c.*132C > A). We report three Mexican families with beta thalassemia intermedia due to different molecular basis; a new single nucleotide mutation involving the last nucleotide of the b-globin chain transcript; and two possible new DNA rearrangements, an a cluster duplication, and a partial b gene deletion.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Three Mexican Families with β thalassemia intermedia with different molecular basis

Ldcr

Fjp

et al. 2019

Genet. Mol. Biol.

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“… 1 Beta thalassemia encompasses a wide range of clinical phenotypes ranging from the severe, transfusion dependent thalassemia major, to the almost asymptomatic thalassemia minor, with the phenotype thalassemia intermedia being intermediate between these 2 extremes. 2 Among the phenotypes associated with alpha thalassemia, the only clinically significant is hemoglobin H disease, which also presents as thalassemia intermedia. 3 …”

mentioning

confidence: 99%

Factors affecting quality of life in children and adolescents with thalassemia in Iraqi Kurdistan

Mikael

Al-Allawi

2018

SMJ

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Objectives:To assess the health related quality of life (HRQoL) in Iraqi Kurd children and adolescents with thalassemia, and identify the factors that affect it.Methods:In the period between May and June 2018, 100 thalassemic patients and 100 healthy subjects between the ages of 6-18 years were enrolled. The patients included 73 with thalassemia major (TM) and 27 with intermedia (TI). Patients were clinically re-evaluated, and the pediatric quality of life inventory (PedsQL) 4.0 was administered by both child and parent reports.Results:The mean HRQoL score of thalassemic patients was significantly lower than that of healthy subjects, with lowest scores in physical functioning. Furthermore, the mean HRQoL of TM was significantly lower than that of TI subgroup. Significantly lower mean HRQoL scores were seen in those taking ≥6 transfusions/year, with hepatitis C infection, with illiterate parents, and those on oral iron chelation. Pearson correlation revealed that HRQoL was negatively associated with age, frequency of transfusions, and serum ferritin, but positively correlated with age at starting transfusion and age at diagnosis. Only age and serum ferritin remained significant by multivariate analysis.Conclusion:This study shows that among Iraqi Kurds with thalassemia, the disease has a significant negative impact on quality of life, with age and serum ferritin being identified as independent predictors. Psychosocial, educational, and patient-centered management programs may be needed to improve HRQoL in this disease.

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“…[ 1 ] Its inheritance is associated with a variety of phenotypes ranging from severe transfusion-dependent thalassemia major to usually asymptomatic thalassemia minor, with an intermedia phenotype in between. [ 2 ] The major phenotype is due to homozygous or compound heterozygous β-thal gene inheritance, while the minor is heterozygous for the mutant allele. The intermedia phenotype genetics are much more complex.…”

Section: Introductionmentioning

confidence: 99%

HBG2 -158 (C>T) polymorphism and its contribution to fetal hemoglobin variability in Iraqi Kurds with beta-thalassemia minor

2018

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PURPOSE: Hemoglobin (Hb) F% is increased in up to half of beta-thalassemia (β-thal) carriers. Several polymorphisms have been linked to such variability in different populations, including HBG2 - 158(C>T) (Xmn I polymorphism) on chromosome 11. To determine the role of this polymorphism in such variability among Iraqi Kurds, the current study was initiated. MATERIALS AND METHODS: A total of 102 consecutive patients diagnosed as β-thal minor were enrolled. The enrollees had their diagnosis based on peripheral blood counts and high-performance liquid chromatography to determine HbA2 and HbF. All enrollees had their DNA extracted by phenol-chloroform method and Xmn I polymorphism detected by restriction fragment length polymorphism-polymerase chain reaction. RESULTS: The mean age (standard deviation [SD]) of the 102 enrollees was 25.4 (14.0) years, and the enrollees included 48 males and 54 females. Xmn I polymorphism was identified in heterozygous state in 46 (45.1%) patients and in homozygous state in one patient (0.98%). Thus, the minor allele frequency of this polymorphism was 0.235 in the studied group. There were no significant differences in red cell indices and HbA2% in carriers of the minor allele compared to noncarriers, while HbF% and absolute HbF concentrations were significantly higher in the former subgroup (P = 0.032 and 0.014, respectively). This polymorphism's contribution to HbF variability was found to be 5.8% in the studied sample. Furthermore, those with HbF ≥2% were 3.2 folds more likely to carry the minor allele. CONCLUSIONS: Xmn I polymorphism is frequently encountered in Iraqi Kurds with β-thal minor, and it is significantly associated with higher fetal hemoglobin in these patients.

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Revisiting beta thalassemia intermedia: past, present, and future prospects

Cited by 24 publications

References 93 publications

Three Mexican Families with β thalassemia intermedia with different molecular basis

Three Mexican Families with β thalassemia intermedia with different molecular basis

Factors affecting quality of life in children and adolescents with thalassemia in Iraqi Kurdistan

HBG2 -158 (C>T) polymorphism and its contribution to fetal hemoglobin variability in Iraqi Kurds with beta-thalassemia minor

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