Abstract

Aims: To identify a novel β globin gene mutation found in a Chinese family, and also to assess its functional consequences.

Methods: Haematological analysis was performed on all family members. The 23 common mutations of β thalassaemia found in Chinese populations were detected by means of a reverse dot blot method. Direct DNA sequencing of polymerase chain reaction (PCR) amplified complete β globin gene was carried out to identify the novel mutation. A real time, one step reverse transcription PCR assay was used to measure β globin mRNA in the reticulocytes of heterozygous patients.

Results: A novel frameshift mutation—an insertion of G between codons 15 and 16 in a homonucleotide run of four guanines—was determined, which generates a new premature chain terminator at the 22nd codon. Relative quantitative analysis of the β globin mRNA in heterozygous subjects demonstrated a 39.83% reduction compared normal controls.

Conclusions: The significantly lower amounts of β globin mRNA found in mutation carriers is probably caused by the rapid nonsense mediated degradation of the mutant mRNA. These data, combined with haematological analysis, suggest that this novel mutation of CDs15/16 (+G) results in a β⁰ thalassaemia phenotype.