Identification of a novel β⁰ ‐ thalassaemia mutation in a greek family and subsequent prenatal diagnosis

Abstract

We present a case in which a Greek couple was considered not to be at risk of having children with homozygous beta-thalassaemia, an assessment based largely on the father's belief that he carried alpha-thalassaemia. After their first child was diagnosed with homozygous beta-thalassaemia, the case was re-assessed and both parents were shown to have the haematological profile of beta-thalassaemia trait. Screening for the common Mediterranean mutations demonstrated that the mother carries the IVS-1 nt 110 G-->A beta(+)-thalassaemia mutation. Direct nucleotide sequencing of PCR-amplified DNA revealed that the father carries a novel beta O-thalassaemia mutation, frameshift codons 9/10 (+T). The couple's second pregnancy was terminated after prenatal testing revealed that the fetus had inherited both parental mutations. This case illustrates the need to confirm the carrier status of individuals prior to assessing their genetic risks, and highlights the importance of being able to identify rare or novel beta-thalassaemia mutations.

First report from Turkey of a rare frameshift mutation codons 9/10 +T in the beta-globin gene

“…To date, at least 39 nucleotide insertions in 3 exons of the β-globin gene that result in a modified C-terminal sequence of the β-globin protein have been reported (http://globin.bx.psu.edu/cgi-bin/ hbvar/query_vars3). Codon 9/10 (+T) insertion mutation was first described in a Greek family by Wave et al in 1994 [6], followed by the report of an Iranian patient of Kurdish origin by Rahimi et al [7]. Herein we present a 30-year-old Arab male with the β-thal trait living in Hatay, Turkey that had β-globin gene codon 9/10 (+T) frameshift mutation, which was noted during premarital genetic screening.…”

Molecular Analysis and Prenatal Diagnosis of Segregating Β-Thalassemia

“…β-thalassemia is a complex and heterogeneous genetic blood disorder that affects millions of people worldwide, with the highest concentration of carriers in the "thalassemia belt" stretching from the Mediterranean to Southeast Asia (1). The condition is caused by mutations in the HBB gene, leading to reduced or absent production of β-globin chains, a crucial component of adult hemoglobin (2).…”