Molecular analysis using DHPLC of cystic fibrosis: increase of the mutation detection rate among the affected population in Central Italy

BMC Medical Genetics

Giuseppe Novelli³  Federica Sangiuolo³  Vincenzina Lucidi²  Anna Maria Nardone³  Silvia Russo¹  Mario Bengala³  Stefano Gambardella¹  Maria Rosaria D'Apice¹ 

[1] Dipartimento di Biopatologia, Università di Roma Tor Vergata, Roma, Italy;Ospedale Pediatrico Bambino Gesù, Roma, Italy;Azienda Ospedaliera Universitaria Policlinico di Tor Vergata, Roma, Italy

关键词: DHPLC;    CFTR mutation screening;    Cystic fibrosis;   

Others  :  1178784
DOI  :  10.1186/1471-2350-5-8

 received in 2003-11-26, accepted in 2004-04-14,  发布年份 2004

【 摘 要 】

Background

Cystic fibrosis (CF) is a multisystem disorder characterised by mutations of the CFTR gene, which encodes for an important component in the coordination of electrolyte movement across of epithelial cell membranes. Symptoms are pulmonary disease, pancreatic exocrine insufficiency, male infertility and elevated sweat concentrations. The CFTR gene has numerous mutations (>1000) and functionally important polymorphisms (>200). Early identification is important to provide appropriate therapeutic interventions, prognostic and genetic counselling and to ensure access to specialised medical services. However, molecular diagnosis by direct mutation screening has proved difficult in certain ethnic groups due to allelic heterogeneity and variable frequency of causative mutations.

Methods

We applied a gene scanning approach using DHPLC system for analysing specifically all CFTR exons and characterise sequence variations in a subgroup of CF Italian patients from the Lazio region (Central Italy) characterised by an extensive allelic heterogeneity.

Results

We have identified a total of 36 different mutations representing 88% of the CF chromosomes. Among these are two novel CFTR mutations, including one missense (H199R) and one microdeletion (4167delCTAAGCC).

Conclusion

Using this approach, we were able to increase our standard power rate of mutation detection of about 11% (77% vs. 88%).

【 授权许可】

   
2004 D'Apice et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

Figure 1.

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