Diagnosis of Fanconi Anemia: Mutation Analysis by Next-Generation Sequencing. (4th April 2012)

• Record Type: Journal Article
• Authors: Ameziane, Najim; Sie, Daoud; Dentro, Stefan; Ariyurek, Yavuz; Kerkhoven, Lianne; Joenje, Hans; Dorsman, Josephine C.; Ylstra, Bauke; Gille, Johan J. P.; Sistermans, Erik A.; de Winter, Johan P.
• Other Names: Meyer Stefan Academic Editor.
• Is Part Of: Anemia. Volume 2012(2012)
• Publication Date: 2012-04-04
• Subjects: Anemia -- Periodicals; 616.152005
• DOI: 10.1155/2012/132856
• Languages: English
• ISSNs: 2090-1267

Abstract

Abstract : Fanconi anemia (FA) is a rare genetic instability syndrome characterized by developmental defects, bone marrow failure, and a high cancer risk. Fifteen genetic subtypes have been distinguished. The majority of patients ( ≈ 85%) belong to the subtypes A ( ≈ 60%), C ( ≈ 15%) or G ( ≈ 10%), while a minority ( ≈ 15%) is distributed over the remaining 12 subtypes. All subtypes seem to fit within the "classical" FA phenotype, except for D1 and N patients, who have more severe clinical symptoms. Since FA patients need special clinical management, the diagnosis should be firmly established, to exclude conditions with overlapping phenotypes. A valid FA diagnosis requires the detection of pathogenic mutations in a FA gene and/or a positive result from a chromosomal breakage test. Identification of the pathogenic mutations is also important for adequate genetic counselling and to facilitate prenatal or preimplantation genetic diagnosis. Here we describe and validate a comprehensive protocol for the molecular diagnosis of FA, based on massively parallel sequencing. We used this approach to identify BRCA2, FANCD2, FANCI and FANCL mutations in novel unclassified FA patients.