Homozygous beta-thalassaemia resulting in the beta-thalassaemia carrier state phenotype

• Published in: British journal of haematology Vol. 88; no. 3; p. 562
• Main Authors: Rosatelli, M C, Pischedda, A, Meloni, A, Saba, L, Pomo, A, Travi, M, Fattore, S, Cao, A
• Format: Journal Article
• Language: English
• Published: England 01-11-1994
• Subjects: Base Sequence; beta-Thalassemia - genetics; DNA - analysis; Female; Genetic Carrier Screening; Heterozygote; Homozygote; Humans; Male; Molecular Sequence Data; Mutation; Pedigree
• ISSN: 0007-1048
• DOI: 10.1111/j.1365-2141.1994.tb05074.x

This paper describes the phenotypic manifestations of a very mild beta-thalassaemia mutation detected in several members of two families of Italian descent. The molecular defect, defined by denaturing gradient gel electrophoresis analysis and direct sequencing, consists of a C-->G substitution at position 844 of IVSII of the beta-globin gene within the consensus sequence of the IVSII acceptor splice site. Heterozygotes for this mutation show a haematological phenotype ranging in severity from silent beta-thalassaemia to that of a mild beta-thalassaemia carrier state, whereas homozygotes have the typical manifestations commonly resulting from heterozygosity for a beta-thalassaemia mutation. Compound heterozygotes for the IVSII nt844 (C-->G) mutation and a severe beta-thalassaemia mutation have the phenotype of thalassaemia intermedia. This paper indicates that the presence of borderline red blood cell indices or HbA2 values should make one suspect the presence of a very mild or silent beta-thalassaemia.