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

• Published in: Clinica chimica acta 2013-01, Vol.415, p.35-40
• Main Authors: Pissard, Serge, Raclin, Valérie, Lacan, Philippe, Garcia, Caroline, Aguilar-Martinez, Patricia, Francina, Alain, Joly, Philippe
• Format: Article
• Language: English
• Subjects: Adult; Base Sequence; beta-Globins - genetics; Cluster; Deletion; Emigrants and Immigrants; Female; Fetal Hemoglobin - genetics; France; Gap-PCR; Genetic Testing; Health Surveys; Hemoglobin A - genetics; Hemoglobinopathies - diagnosis; Hemoglobinopathies - genetics; HPFH; Humans; Male; Molecular Sequence Data; Multigene Family; Mutagenesis, Insertional; Polymerase Chain Reaction; Sequence Analysis, DNA; Sequence Deletion; Thalassemia; Urban Population; β-globin
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2012.08.030

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. 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. 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, −1.39kb, Indian −619bp and −468bp. Interestingly, three new deletions were fully characterized: a −7719bp deletion, a −27,825bp deletion with a 25bp insertion and a −125bp deletion. The present study emphasizes the importance to detect deletions in the β-globin gene cluster, particularly for at risk couples. The new −27,825bp deletion illustrates the complexity to understand the transcriptional regulation of fetal to adult hemoglobin switch. ► Prevalent deletions were the Ghanian HPFH-2, the Sicilian and Spanish (δβ)0-thal. ► Other deletions were found such as HPFH-3, HPFH-1, Filipino, Senegalese and Corfu. ► New deletions were: a −7719bp, a −27,825bp with a 25bp insertion and a −125bp.