Identification of rare hemoglobin variant (Hb Fairfax) causing dominant β-thalassemia phenotype in an Iranian family

Autor: Mohammad Esmaeil Akbari, Mina Izadyar, Mohammad Hamid
Přispěvatelé: Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University [Tehran], Tehran Medical Genetics Laboratory, Tehran Medical Genetics Laboratory [Iran], Molecular Medicine Division, Biotechnology Research Center, Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Department of Pediatric Hematology, Markase Tebbi Koodakan (Children Medical Center), Tehran University of Medical Sciences
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Annals of Hematology
Annals of Hematology, Springer Verlag, 2011, 90 (3), pp.349-51. ⟨10.1007/s00277-010-1003-4⟩
ISSN: 0939-5555
1432-0584
DOI: 10.1007/s00277-010-1003-4⟩
Popis: Dear Editor, More than 900 hemoglobin (Hb) variants have been reported, and most variants are caused by mutations in the αor β-globin gene clusters [1]. Clinically, most of hemoglobin variants are asymptomatic, but some variants are unstable, with altered oxygen affinity, or have a thalassemic phenotype (Hb Var database—http://globin. cse.psu.edu/globin/hbvar). Hemoglobin Fairfax is a rare Hb variant, which has been reported only in an African-American child. This hemoglobin results from 15-base-pair tandem duplication of GAGCTGCACTGTGAC sequences inserted between codons 94 and 95, coding an additional Glu-Leu-His-CysAsp amino acids [2, 3]. We report on the hematological and molecular features of hemoglobin Fairfax for the first time in two members (mother and her daughter) of an Iranian family. This family was referred for prenatal diagnosis for β-thalassemia mutations. Red blood cell indices and Hb analysis were carried out according to standard methods. Tests for unstable Hb using isopropanol precipitation showed positive results in both patients. After obtaining a written informed consent, molecular studies were conducted on genomic DNA isolated from peripheral blood cells by a salting out procedure [4]. For identifying αthalassemia genotype, common deletional mutations were studied as previously described [5] with no mutation in αthalassemia genotype. Triplication of α-globin genes was also excluded. Moreover, the entire β-globin gene was amplified and the DNA sequenced with the use of a primer set encompassing exons 1 and 2 (for fragment A: Beta1F 5′-GGGCCAAGAGATA TATCTTAG-3′, Beta1R 5' AATGACATGAACTTA ACCATAG-3′) and another encompassing exon 3 (fragment B: Beta2F 5′-GCAC CATTCTAAAGAATAACAG-3′, Beta2R 5′-GTTTGAAC TAGCTCTTCATTTC-3′). The sequencing reactions were performed by the chain termination method on ABI 3730 XL sequencer (Primm, Milan, Italy), as described elsewhere [6, 7]. The nucleotide numbering is based on GenBank accession number U01317. The hematological and molecular features of hemoglobin Fairfax in the index patient and her mother aged 5 and 29 years old, respectively, are summarized in Table 1. The index case with severe hemolytic anemia, marked splenomegaly, and blood transfusion dependency (every 20 days) receives iron chelating therapy (Desferal) four times a week. She had no other thalassemic features. M. T. Akbari Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111, Iran
Databáze: OpenAIRE
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