Characterization of three new deletions in the β-globin gene cluster during a screening survey in two French urban areas

Abstract

Background: Deletions represent about 5% of the mutations in the β-globin gene cluster. We report here the screening for such deletions in the two French urban areas of Paris and Lyon between 2003 and 2010.

Methods: Semi-quantitative PCR methods were used for the first screening of deletions. Thereafter, a specific gap-PCR, eventually followed by DNA sequencing, was used for precise identification.

Results: 285 patients bore a deletion or recombination event in the β-globin gene cluster. Hbs Lepore or anti-Lepore were detected in 99 patients. Among the remaining 186 patients, 132 bore a deletion that could be fully identified. The most prevalent deletions were the Ghanaian HPFH-2 (n=46), the Sicilian (δβ)(0)-thal (n=22) and the Spanish (δβ)(0)-thal (n=12). The other characterized deletions were the: HPFH-3, HPFH-1, Filipino, Senegalese, Corfu, Kabilian, -1.39 kb, Indian -619 bp and -468 bp. Interestingly, three new deletions were fully characterized: a -7719 bp deletion, a -27,825 bp deletion with a 25 bp insertion and a -125 bp deletion.

Conclusions: The present study emphasizes the importance to detect deletions in the β-globin gene cluster, particularly for at risk couples. The new -27,825 bp deletion illustrates the complexity to understand the transcriptional regulation of fetal to adult hemoglobin switch.