The β+ IVS, I‐NT no. 6 (T→ C) thalassaemia in heterozygotes with an associated Hb Valletta or Hb S heterozygosity in homozygotes from Malta

Abstract

Summary. In vitro DNA amplification and dot blot analysis with synthetic allele specific oligonucleotides (ASO) identified the β IVS, I‐6 (T→C) thalassaemia in 78% of 32 chromosomes from 16 β‐thalassaemia homozygotes in Malta. The preponderance of a single thalassaemia mutation in one population is unusual. The β+ IVS, I‐6C thalassaemia mutation was also found in three carriers who had an associated β globin heterozygosity, i.e. Hb Valletta (or α2β287PRO) or Hb S (or α2β26VAL). The proportion of Hb A in these cases (av. = 29.7%) provided objective documentation of the relatively mild effect of this mutation on in vivo globin gene expression. However, the expression of homozygous disease was more severe in developing children compared to adults. The β+ IVS, I‐6C mutation complicates population testing because heterozygotes can have Hb A2 levels below those classically associated with β thalassaemia.