ORIGINAL ARTICLE

⁰ Thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated globin genes

S-Q Jia¹, J Li², Q-H Mo¹, C Liao², L-Y Li¹, X-M Xu¹

¹ Department of Medical Genetics, First Military Medical University, Guangzhou 510515, Guangdong, PR China
² Division of Medical Genetics, Guangzhou Municipal Maternity and Child Healthcare Hospital, Guangzhou 510180, Guangdong, PR China

Correspondence to:
Correspondence to:
Dr X-M Xu
Department of Medical Genetics, First Military Medical University, Tonghe 510515, Guangzhou, Guangdong, PR China; gzxuxm{at}pub.guangzhou.gd.cn

Aims: To characterise a novel 11.1 kb deletion that eliminated both of the duplicated globin genes, giving rise to a typical ⁰ thalassaemia phenotype in four carriers from a Chinese family.

Methods: Haematological investigations were carried out on all family members. The seven common forms of thalassaemia were screened for by the polymerase chain reaction (PCR) and Southern blotting was used to analyse the globin gene cluster. DNA sequence analysis of the entire 1 and 1 globin gene region was carried out and reverse transcription (RT)-PCR was used to investigate the transcription levels of the and ß globin genes.

Results: The breakpoints were found to lie between coordinates 31695–31724 and 42846–42867 of the 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 globin gene in heterozygotes comparable with that of SEA deletion heterozygotes, confirming no output of globin from the linked pair of 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 thalassaemia in the Chinese population.

Keywords: thalassaemia; globin gene; legitimate recombination; mutation detection

Abbreviations: Hb, haemoglobin; nt, nucleotides; PCR, polymerase chain reaction; RT, reverse transcription

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