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We have used restriction site-dependent polymerase chain reaction (PCR)-based methodology for detection of the α-globin polyadenylation (poly A) signal mutation, AATAAA>AATA- - and Hb Sun Prairie [α130(H13)Ala→Pro, GCT>CCT (α2)] mutation. The former mutation produces Hb H disease in the homozygous state and occurs frequently in the Indian population. It was detected in nine of 77 putative α-thalassemia (α-thal) patients and in three of 13 β-thal intermedia patients tested. Four of the nine α-thal patients were homozygotes for the mutation. The Hb Sun Prairie mutation was confirmed in two α-thal patients, one of whom was a homozygote and the other a heterozygote. [ABSTRACT FROM AUTHOR]

Haemoglobin (Hb) Sun Prairie (α2-globin cd130,CT→CT, Ala→Pro) is detected in three unrelated chromosomes, in association with a C→T transition in the 5′-untranslated region (UTR), two bases upstream from the translation start site. Reported inversion ofα/β-mRNA ratio observed in Hb Sun Prairie mutants might stem from the second mutation and should be investigated. Molecular modelling studies indicate that the 130th residue ofα-globin faces primarily the central cavity of the molecule and is not in contact with anyβ-chain residue; further, no significant disruption of the Hb structure because of the Sun Prairie mutation is discernible. Depression of translation because of the second mutation of a conserved base in the 5′-UTR might explain the observed clinical severity. [ABSTRACT FROM AUTHOR]