Alpha-Thalassaemia in Association with Beta-Thalassaemia Patients in Malaysia: A Study on the Co-Inheritance of Both Disorders

Wee, Yong-Chui; Tan, Kong Wai; Kuldip, K.; Tai, Kei‐Sing; George, Elizabeth; Tan, Pei; Chia, Po Ying; Subramaniam, Rajeshwari; Yap, Sook Fan; Tan, Ji

doi:10.1159/000113874

Cited by 13 publications

(14 citation statements)

References 37 publications

(24 reference statements)

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“…Wee et al(2008) found that incidence of α-thal in the β-thal carriers in Malaysian population was 12.7% (41/322), with the frequency of carrier was 7.8% of the SEA deletion, 3.7% of the –α 3.7 , 0.9% of Hb Constant Spring and 0.3% of the –α 4.2 23. Fallah et al also reported that –α 3.7 was the most frequent α-globin mutation, co-inheritance of –ααα anti3 with β-thal frequently occurred in general population of the Iran and has adverse clinical manifestation in β-thalassemia 24…”

Section: Discussionmentioning

confidence: 99%

Alpha thalassemia deletions found in suspected cases of beta thalassemia major in Pakistani population

et al. 2017

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Background & Objective:Alpha (α) thalassemia is a hereditary disorder and is caused by deletions or mutations in globin genes. It is present in two clinically significant forms: hemoglobin Bart hydrops fetalis (Hb Bart) syndrome and hemoglobin H (HbH) disease. It is highly prevalent in South-East Asia or Mediterranean countries. The most common deletion reported in alpha thalassemia in Pakistani population was –α3.7 with a frequency of 8.3%, and the rare forms were –α4.2 (0.2%) and αααanti3.7 (0.9%). In our study, diagnosis of severe anemia cases without any α and β mutations or deletions were made by using extended alpha thalassemia deletions panel. The main objective of this study was to determine the prevalence and to study the spectra of alpha thalassemia gene deletions in beta thalassemia patients with the use of an extended panel including −−SEA, −−FIL, −−MED, −−20.5, −−THAI in addition to –α3.7, –α4.2 & -αααanti3.7.Methods:The samples were collected in ethylenediaminetetraacetic acid (EDTA) vacutainers. A total of 156 samples were analyzed for alpha thalassemia mutations. This cohort included 121 samples of beta thalassemia major, nine samples of beta thalassemia minor and 26 without any evidence of beta thalassemia mutations. DNA was extracted with Qiagen extraction kit. The primers for determination of different subsets of alpha thalassemia deletions were included. PCR amplification was performed and result interpreted on agarose gel.Results:Co-inheritance of alpha thalassemia (–α3.7, –α4.2) with homozygous beta thalassemia was detected in 30% cases of studied cohort (37 out of 121). The most common found was –α3.7 deletion (35/37) as single/double deletions or in combination with -αααanti3.7. In undiagnosed cases screened for beta thalassemia major, we found Mediterranean (–αMED) deletion at specifically 875 bp on agarose gel. This is distinctive finding in case of detecting –αMED instead of any other deletion from Pakistan.Conclusion:Alpha thalassemia deletions (–α3.7, –α4.2) are the common co-inherited deletions found in beta thalassemia major patients. On the basis of results, we propose an extended alpha thalassemia genetic mutation panel should be used for screening of children presenting with anemia with suspicion of haemoglobinopathy.

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Section: Discussionmentioning

confidence: 99%

Alpha thalassemia deletions found in suspected cases of beta thalassemia major in Pakistani population

et al. 2017

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“…The extent of anemia in thalassemia is determined by the ratio of α- to β-peptides. Coinheritance of α-thalassemia with β-thalassemia is mainly seen in patients with thalassemia intermedia [22,23]. Peptide analyses have shown that in patients coinheriting β-thalassemia major and HbH disease (– Med /–α 3.7 ), α-/non-α-globin chain biosynthesis was balanced and patients do not require blood transfusion, although they have marked anemia as hemoglobin is maintained at 85–95 g/l [24].…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin H Disease in Guangxi Province, Southern China: Clinical Review of 357 Patients

et al. 2010

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The clinical characteristics of 357 patients with hemoglobin H (HbH) disease from the Guangxi province of Southern China were studied. One hundred and ninety-one (53.3%) patients were diagnosed with HbH-Constant Spring, 19 were diagnosed with HbH Westmead. Ten patients were shown to have coinherited HbH-Constant Spring/QS with a β-thalassemia mutation. Coinheritance of the β-thalassemia gene does not alleviate anemia (8.2 ± 2.3 vs. 7.6 ± 1.7 g/dl, p = 0.276), or influence age at diagnosis (20.2 ± 19.6 vs. 12.9 ± 11.0 years, p = 0.276). Ferritin levels were significantly higher in the group of patients with the nondeletional form of the disease (475 ± 719 vs. 249 ± 264 ng/ml, p = 0.005).

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“…They have a wide range of skin color, wavy hair and are generally taller than the Negrito (Ang et al 2012). Due to the habitats and hunter-gatherer lifestyle, all three Orang Asli groups are routinely exposed to medical stresses including malnutrition and persistent exposure to communicable diseases such as leptospirosis, smallpox, and of notably, malaria (Baer et al 1976;Eng et al 1973;Wee et al 2008;Bellwood 2007, page 256). Malaria exerts one of the strongest known evolutionary pressures on the human genome, giving rise to common Mendelian diseases such as sickle-cell disease, thalassemia and glucose-6-phosphatase dehydrogenase (G6PD) deficiency that paradoxically protect against malaria parasitic invasion (Clark et al 2009;Hanchard et al 2007;Kwiatkowski and Luoni 2006;Panda et al 2012;Rout et al 2011;Ruwende et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia

Liu

Yunus

et al. 2015

Hum Genet

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The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.

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Alpha-Thalassaemia in Association with Beta-Thalassaemia Patients in Malaysia: A Study on the Co-Inheritance of Both Disorders

Cited by 13 publications

References 37 publications

Alpha thalassemia deletions found in suspected cases of beta thalassemia major in Pakistani population

Alpha thalassemia deletions found in suspected cases of beta thalassemia major in Pakistani population

Hemoglobin H Disease in Guangxi Province, Southern China: Clinical Review of 357 Patients

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia

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