%0 Journal Article
%T Diagnosis of Fanconi Anemia: Mutation Analysis by Next-Generation Sequencing
%A Najim Ameziane
%A Daoud Sie
%A Stefan Dentro
%A Yavuz Ariyurek
%A Lianne Kerkhoven
%A Hans Joenje
%A Josephine C. Dorsman
%A Bauke Ylstra
%A Johan J. P. Gille
%A Erik A. Sistermans
%A Johan P. de Winter
%J Anemia
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/132856
%X 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.
%U http://www.hindawi.com/journals/ane/2012/132856/