Molecular diagnosis of α‐thalassemia in a multiethnic population

Gilad, Oded; Shemer, Orna Steinberg; Dgany, Orly; Krasnov, Tanya; Nevo, Michal; Noy-Lotan, Sharon; Rabinowicz, Ron; Amitai, Nofar; Ben‐Dor, Shifra; Yaniv, Isaac; Yacobovich, Joanne; Tamary, Hannah

doi:10.1111/ejh.12866

Cited by 23 publications

(14 citation statements)

References 44 publications

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“…Primers designed for amplification of the coding regions and the exon-intron junctions were based on the genomic sequence obtained from databases (http://www.ncbi.nlm.nih.gov/). Sequencing was performed as previously described [21].…”

Section: Methodsmentioning

confidence: 99%

Alpha-Thalassemia Carrier due to –α<sup>3.7</sup> Deletion: Not So Silent

et al. 2020

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Background/Objective: Alpha-thalassemia is one of the most prevalent genetic diseases, with the-α 3.7 deletion being the most common mutation. Molecular studies have suggested mechanisms to explain the mild phenotype of "silent carrier" heterozygotes. However, the correlation between the clinical laboratory picture and the-α 3.7 heterozygous state remains unclear, thus we chose to investigate. Methods: We analyzed the medical files of 192 children evaluated for microcytosis at our tertiary center between 2007 and 2017 and diagnosed as heterozygotes for the-α 3.7 deletion. Additional α-thalassemia mutations, iron deficiency anemia, and β-thalassemia were ruled out. Laboratory parameters were compared to age-and sex-matched reference values. Results: The-α 3.7 carriers had significantly lower Hb and mean corpuscular volume (MCV) than the reference population, and significantly higher red blood cell counts across all age groups. The greatest reduction in Hb level appeared among male adolescents, while MCV was consistently 2 SDs lower than normal in most patients older than 2 years. Conclusion: Heterozygosity for the-α 3.7 deletion was associated with clinically significant microcytosis and mild anemia in our pediatric population. In the absence of iron deficiency and β-thalassemia, this finding provides a diagnosis for mild microcytic anemia, making additional investigations of microcytosis unnecessary.

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Section: Methodsmentioning

confidence: 99%

Alpha-Thalassemia Carrier due to –α<sup>3.7</sup> Deletion: Not So Silent

et al. 2020

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“…The disease severity was classified as silent carrier, α-thalassemia trait and HbH disease depending on the number, type and location of mutations detected, in addition to the clinical phenotype and presence of HbH inclusions or H band on HPLC [1,17,20] Data are presented as means ± SD or as percentages as appropriate. Statistical differences between mean values among the major groups were tested using Student t test.…”

Section: Methodsmentioning

confidence: 99%

Spectrum of Alpha Thalassemia Alleles in Kuwait

Adekile

Sukumaran

Thomas

et al. 2020

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Background: The frequency of alpha thalassemia trait is about 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is a report of the patients who were referred for molecular diagnosis over a 20-year period. Methods: Blood samples from suspected cases were sent to the Hemoglobin Research Laboratory of the Department of Pediatrics, Kuwait University. A retrospective study of the molecular characterization of samples from 1994 to 2015 was carried out. The alpha globin genotypes were determined by a combination of PCR, allele-specific oligonucleotide hybridization and reverse dot-blot hybridization (Vienna Lab Strip Assay). Results: 400 samples were characterized and analyzed from individuals aged <1 month to 80 years, with a median of 6 years (~60% children and adolescents). Most (90.8%) were Kuwaiti nationals. The common genotype was homozygosity for the polyadenylation-1 mutation (αPA-1α/α PA-1α) in 33.3%, followed by heterozygosity (αα/α PA-1α) for the same mutation in 32.3%. The PA-1 was therefore the most frequent allele (0.733). The frequency of the α0, –MED was 0.19. Rare alleles that were found in very low frequencies included the α0 (--FIL) in a Filipino child, Hb Constant Spring, Hb Adana,and Hb Icaria. Conclusion: There is a wide variety of alpha thalassemia alleles among Kuwaitis, but the nondeletional PA-1 is by far the most common cause of moderate to severe HbH disease phenotype. The α0 (–MED) allele is also encountered, which has implications for pre-marital counselling especially the possibility of having babies with alpha thalassemia major (Barts hydrops fetalis).

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“…The disease severity was classified as silent carrier, α-thalassemia trait or HbH disease depending on the number, type and location of mutations detected, in addition to the clinical phenotype and presence of HbH inclusions or H bands on HPLC [ 1 , 17 , 20 ].…”

Section: Methodsmentioning

confidence: 99%

Alpha thalassemia genotypes in Kuwait

et al. 2020

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Background: The frequency of the alpha thalassemia trait is approximately 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is a report of patients who were referred for molecular diagnosis over a 20-year period. Methods: This is a retrospective study of the α-globin genotypes obtained in the Hemoglobin Research Laboratory of the Department of Pediatrics, Kuwait University from 1994 to 2015. Genotyping was performed by a combination of PCR, allele-specific oligonucleotide hybridization and reverse dot blot hybridization (Vienna Lab Strip Assay). Results: Four hundred samples were characterized and analyzed from individuals aged < 1 month to 80 years, with a median of 6 years from 283 unrelated families. Most (90.8%) were Kuwaiti nationals. The commonest genotype was homozygosity for the polyadenylation-1 mutation (α PA-1 α/α PA-1 α) in 33.3% of the samples, followed by heterozygosity (αα/α PA-1 α) for the same mutation in 32.3%. PA-1 was therefore the most frequent allele (0.59). The frequency of the α 0 (−-MED) allele was 0.017. Rare alleles that were found in very low frequencies included α 0 (−-FIL) in a Filipino child, Hb Constant Spring, Hb Adana, and Hb Icaria. Conclusion: There is a wide variety of alpha thalassemia alleles among Kuwaitis, but nondeletional PA-1 is by far the most common cause of the moderate to severe HbH (β4 tetramer) disease phenotype. The α 0 (− MED) allele is also encountered, which has implications for premarital counseling, especially for the possibility of having babies with alpha thalassemia major (Barts hydrops fetalis).

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Molecular diagnosis of α‐thalassemia in a multiethnic population

Abstract: Our work constitutes the largest group of patients with α-thalassemia originating in the Mediterranean whose clinical characteristics and molecular basis have been determined. We suggest a diagnostic algorithm that leads to an accurate molecular diagnosis in multiethnic populations.

Cited by 23 publications

References 44 publications

Alpha-Thalassemia Carrier due to –α<sup>3.7</sup> Deletion: Not So Silent

Alpha-Thalassemia Carrier due to –α<sup>3.7</sup> Deletion: Not So Silent

Spectrum of Alpha Thalassemia Alleles in Kuwait

Alpha thalassemia genotypes in Kuwait

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