Abstract

Aims: To characterise a novel 11.1 kb deletion that eliminated both of the duplicated α globin genes, giving rise to a typical α⁰ thalassaemia phenotype in four carriers from a Chinese family.

Methods: Haematological investigations were carried out on all family members. The seven common forms of α thalassaemia were screened for by the polymerase chain reaction (PCR) and Southern blotting was used to analyse the α globin gene cluster. DNA sequence analysis of the entire α1 and α1 globin gene region was carried out and reverse transcription (RT)-PCR was used to investigate the transcription levels of the α and β globin genes.

Results: The breakpoints were found to lie between coordinates 31695–31724 and 42846–42867 of the α globin gene cluster (NG_000006), with a total of about 11 135 nucleotides deleted. These sequences are involved in (CA)_n repeats, suggesting a homologous recombination event. RT-PCR analysis gave a transcription level of the α globin gene in heterozygotes comparable with that of SEA deletion heterozygotes, confirming no output of α globin from the linked pair of α globin genes. The heterozygosity for this novel deletion was confirmed by PCR diagnosis in all four carriers from this family.

Conclusions: This rare mutation constitutes an additional heterogeneous defect causing α thalassaemia in the Chinese population.