A single nucleotide deletion in codon 123 of the β‐globin gene causes an inclusion body β‐thalassaemia trait: a novel elongated globin chain βMakabe

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Abstract
Summary. The β‐globin gene from a Japanese individual with an inclusion body β‐thalassaemia trait has been characterized by gene cloning and DNA sequencing. An adenine deletion was detected at the first position of codon 123 (ACC‐CC) of one allele whereas the other allele had a normal sequence. Heterozygosity for this mutation in the patient was confirmed by Southern blots of the genomic DNA digested with HphI, the recognition site of which is eliminated by this deletion. This one base deletion results in the shift of a reading frame in such a manner that the normal termination codon is out of phase. This frameshift mutation results in the synthesis of an elongated β‐globin chain with 10 extra amino acid residues and with an altered C‐terminus. Analysis of labelled globin chains using CM‐cellulose column chromatography failed to demonstrate any abnormal protein, thereby suggesting that the β‐globin chain variant is highly unstable and probably degrades rapidly after synthesis. This event will lead to an accumulation of free α‐chains precipitating in the red blood cells and an inclusion body β‐thalassaemia phenotype would ensue.