Molecular analysis of a large novel deletion causing α+-thalassemia.

BACKGROUND: α-thalassaemia is an inherited blood disorder caused by mutations in the α-globin gene cluster. Recognizing the pathogenic α-globin gene mutations associated with α-Thalassemia is of significant importance to thalassaemia's diagnosis and management. METHODS: A family with α-thalassaemia from Fujian, China was recruited for this study. The phenotype was confirmed through haematological analysis. Commercially available Gap-PCR genotypic methods were employed to identify the known deletions causing α-thalassemia. MLPA analysis was used to study the novel mutations; this was then confirmed through DNA sequencing and bioinformatics analysis. RESULTS: The proband of the family belonged to Southeast Asian type (--SEA) thalassaemia. None of the known mutations associated with α-thalassaemia were detected in this family's genetics, whereas a novel 6.9 kb deletion (16p13.3 g.29,785-36,746) covering the α2 gene on the globin gene cluster was identified with MLPA and confirmed through Sanger Sequencing. This data led us to propose a novel pathogenic deletion associated with α-thalassemia: -α6.9 /--SEA. CONCLUSIONS: A novel α-thalassaemia deletion was identified in members of a Chinese family and subsequently analyzed. This finding has helped broaden the spectrum of pathogenic mutations leading to the development of α-thalassaemia, paving the way for improved disease diagnosis and management.

Identification of a new ß-thalassaemia variant Term CD+32(HBB: c.32A>C) in two Chinese families.

AIMS: ß-Thalassaemia is an inherited blood disorder caused by mutations in the ß-globin gene cluster. Molecular characterisation of ß-thalassaemia is essential for its diagnosis and management. More and more rare and novel mutations have been reported. METHODS: Two Chinese families with ß-thalassaemia from Fujian Province were recruited in this study. The phenotypes of the probands were confirmed through haematological analysis. Routine molecular analysis of thalassaemia was employed to identify the common mutations of thalassaemia. The rare and novel mutations were detected by direct DNA sequencing. RESULTS: In family 1, the proband, a Chinese woman aged 31 years, showed elevated level of haemoglobin A2 (HbA2). No common mutations associated with ß-thalassaemia were detected, whereas a rare mutation Term CD+32(HBB: c.32A>C) was identified through DNA sequencing. Subsequent investigation of the ß-thalassaemia mutation in her family showed that her mother, her brother as well as her nephew also carried this mutation. In addition, both the proband's husband and her son carrying the rare --THAI mutation exhibited decreased levels of MCH, MCH and HbA2. In family 2, the proband, a child aged 1 year, showed elevated level of HbA2, but had no common mutations of ß-thalassaemia. The proband was identified carrying the mutation Term CD+32(HBB: c.32A>C), which was inherited from his mother. CONCLUSIONS: In this study, we first report a rare ß-thalassaemia mutation in Fujian Province, Southeast China. Moreover, our study also identified this rare mutation in humans. This finding has helped broaden the spectrum of ß-thalassaemia mutations in our region and suggested that this rare mutation may be more prevalent in the Chinese population.