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Molecular, haematological and clinical studies of a silent β‐gene C → G mutation at 6 bp 3′ to the termination codon (+1480 C → G) in twelve Greek families
Author(s) -
Maragoudaki,
Vrettou,
Kanavakis,
TraegerSynodinos,
MetaxotouMavrommati,
Kattamis
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00966.x
Subject(s) - mutation , genetics , compound heterozygosity , biology , microbiology and biotechnology , untranslated region , gene , allele , globin , stop codon , hemoglobinopathy , heterozygote advantage , hemolytic anemia , messenger rna , immunology
We report the clinical, haematological, biosynthetic and molecular data of 12 β‐thalassaemia intermedia patients and their heterozygous parents, all of whom carried a rare C → G mutation at nucleotide position 6 3′ to the termination codon (term. cd +6 C → G) in the 3′ untranslated region (3′ UTR) of the β‐globin gene (+1480 C → G). This mutation has been reported previously in a single β‐thalassaemia intermedia patient of Greek origin. The 12 patients of the present study had the clinical phenotype of mild non‐transfusion‐dependent thalassaemia intermedia, preserving haemoglobin levels around 9 g/dl and haemoglobin F levels < 25%. All were compound heterozygotes for the +1480 C → G mutation and common severe β‐thalassaemia mutations. The haematological parameters of heterozygotes with this mutation were within the normal range with the exception of a slightly raised α/non‐α‐globin chain synthesis (1.2–1.9). mRNA analysis demonstrated a 20–34% reduction in mRNA levels associated with the +1480 C → G mutation compared to normal β‐globin alleles. These findings confirm that the C → G mutation at position 6 3′ to the termination codon is a mild β‐thalassaemia mutation causing slight reduction in β‐globin mRNA levels and β‐globin chain synthesis. It becomes clinically relevant when co‐inherited with a severe β‐thalassaemia mutation in trans .