Diagnosis of Fanconi Anemia: Mutation Analysis by Next-Generation Sequencing

Najim Ameziane, Daoud Sie, Stefan Dentro, Yavuz Ariyurek, Lianne Kerkhoven, Hans Joenje, Josephine C. Dorsman, Bauke Ylstra, Johan J. P. Gille, Erik A. Sistermans, Johan P. de Winter
2012 Anemia  
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
more » ... s 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 identifyBRCA2,FANCD2,FANCIandFANCLmutations in novel unclassified FA patients.
doi:10.1155/2012/132856 pmid:22720145 pmcid:PMC3374947 fatcat:4jn7hvnwbravvnu23zlkrz7rm4