Determination of the breakpoint and molecular diagnosis of a common α‐thalassaemia‐1 deletion in the Indian population

Abstract

Summary. The previously described South African type a-thalassaemia-1 mutation was identified in Indian HbH patients using a polymerase chain reaction (PCR) strategy. A multiplex PCR assay was devised to detect heterozygotes and homozygotes. This a-thalassaemia-1 mutation was found to be the commonest determinant causing HbH disease in this population. In one family this mutation was found in combination with a novel splice donor mutation a2 IVS I-1 (G fi A). Characterization of the breakpoint junction sequence revealed, in addition to a 23 kb deletion, that there was an addition of 160 bp bridging the breakpoints. Similar to other deletions in the a-globin gene cluster, there is an Alu repeat-mediated mechanism for the origin of the deletion. Keywords: a-thalassaemia, PCR, India, AluThe a-thalassaemias are genetic defects characterized by the decrease or complete suppression of synthesis of the a-globin polypeptide chains of haemoglobin. They are the most common single-gene diseases in the world. The a-globin genes are duplicated (a1 and a2) and located within the a gene cluster f2)wf1)wa2)wa1)a2)a1)h1 on the distal short arm region of chromosome 16 (Higgs et al, 1989). This cluster contains four genes and three pseudogenes. Deletions of one ()a) or both () ) )) of these cis-linked genes are the most common causes of the a-thalassaemias. Around 25 different two-gene cis deletions () )) and eight single-gene deletions ()a)

High frequency of deletional α‐thalassemia in β‐thalassemia trait: Implications for genetic counseling

“…A previous study from South India also did not find a high frequency of this deletion [10]. In laboratories with financial constraints, this mutation detection may be omitted.…”

Microcytic hypochromic anemia patients with thalassemia : Genotyping approach

“…[13][14][15] The commonest type of α-thalassemia seen in Iran is -α 3.7 deletion. At our hospital, the overall frequencies of α-thalassemia and β-thalassemia among microcytic, hypochromic anemia patients are 57% and 25.8%, respectively Hadavi et al [16] have reported the prevalence of -α 3.7 deletion to be 30.2% in the population of Iran (87 million).…”

Phenotypic Heterogeneity of Asian Indian Inversion Deletions Gγ(Aγδβ)0 Breakpoint A and Breakpoint B

“…DNA extraction was done by phenol-chloroform method. Molecular study for alpha deletions and beta mutations were done according to published literatures [10][11][12][13][14]. Asian Indian inversion-deletion GcAc(db)0-thalassemia type A and type B mutations were identified according to Craig et al [15] by Gap-PCR.…”