title: Diverse phenotypes and transfusion requirements due to interaction of β-thalassemias with triplicated α-globin genes.
abstract: Co-inheritance of triplicated α-genes can alter the clinical and hematological phenotypes of β-thalassemias. We evaluated the phenotypic diversity and transfusion requirements in β-thalassemia heterozygotes, homozygotes, and normal individuals with associated α-gene triplication. Clinical and hematological evaluation was done and the β-thalassemia mutations characterized by a covalent reverse dot blot hybridization/amplification refractory mutation system. Alpha-globin gene triplication was assessed by multiplex PCR. During the last 2.5 years, 181 β-thalassemia patients and β-thalassemia carriers with an unusual clinical presentation were referred to us for screening for the presence of associated α-globin gene triplication. Twenty-nine of them had associated α-gene triplication (3 β-thalassemia homozygotes or compound heterozygotes and 26 β-thalassemia heterozygotes). One β-thalassemia compound heterozygote [IVS 1-5 (G → C) + CD 41/42 (-CTTT)] was anemic at birth and required blood transfusions unusually early by 6 weeks of age. The second patient (4.5 years) was also clinically severe and became transfusion dependent in spite of having one mild β-thalassemia mutation [Capsite +1 (A → C)]. The third case (3.5 years) who was homozygous for a mild β-gene mutation [-88 (C → T)] with α gene triplication was untransfused. The 26 β-thalassemia heterozygotes with associated triplicated α-genes presented variably, with a β-thalassemia intermedia-like presentation. While screening the family members of all these cases, we found another 10 β-thalassemia heterozygotes and 9 normal individuals with α-globin gene triplication; however, all of them were asymptomatic. Beta-thalassemia carriers, homozygotes, and compound heterozygotes with an unusual presentation should be screened for the possible presence of associated α-globin gene triplication which could influence the clinical and hematological presentation.
authors: National Institute of Immunohaematology, 13th Floor, New MS Building, KEM Hospital Campus, Parel, Mumbai, 400012, India.
authors: Pallavi R
authors: PR
authors: Mehta
authors: National Institute of Immunohaematology, 13th Floor, New MS Building, KEM Hospital Campus, Parel, Mumbai, 400012, India.
authors: Dipti S
authors: DS
authors: Upadhye
authors: National Institute of Immunohaematology, 13th Floor, New MS Building, KEM Hospital Campus, Parel, Mumbai, 400012, India.
authors: Pratibha M
authors: PM
authors: Sawant
authors: National Institute of Immunohaematology, 13th Floor, New MS Building, KEM Hospital Campus, Parel, Mumbai, 400012, India.
authors: Manju S
authors: MS
authors: Gorivale
authors: National Institute of Immunohaematology, 13th Floor, New MS Building, KEM Hospital Campus, Parel, Mumbai, 400012, India.
authors: Anita H
authors: AH
authors: Nadkarni
authors: Hematology Department, KEM Hospital, Parel, Mumbai, 400012, India.
authors: Chandrakala
authors: C
authors: Shanmukhaiah
authors: National Institute of Immunohaematology, 13th Floor, New MS Building, KEM Hospital Campus, Parel, Mumbai, 400012, India.
authors: Kanjaksha
authors: K
authors: Ghosh
authors: National Institute of Immunohaematology, 13th Floor, New MS Building, KEM Hospital Campus, Parel, Mumbai, 400012, India. colahrb@gmail.com.
authors: Roshan B
authors: RB
authors: Colah
mesh_terms: D001803:Blood Transfusion; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D010641:Phenotype; D055542:alpha-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics* / Q000628:therapy*
chemical_list: D055542:alpha-Globins
keywords: Beta-thalassemia; Blood transfusion; Clinical presentation; α-Gene triplication