TY - JOUR T1 - Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology. JF - Haematologica Y1 - 2014 A1 - De Rocco, Daniela A1 - Bottega, Roberta A1 - Cappelli, Enrico A1 - Cavani, Simona A1 - Criscuolo, Maria A1 - Nicchia, Elena A1 - Corsolini, Fabio A1 - Greco, Chiara A1 - Borriello, Adriana A1 - Svahn, Johanna A1 - Pillon, Marta A1 - Mecucci, Cristina A1 - Casazza, Gabriella A1 - Verzegnassi, Federico A1 - Cugno, Chiara A1 - Locasciulli, Anna A1 - Farruggia, Piero A1 - Longoni, Daniela A1 - Ramenghi, Ugo A1 - Barberi, Walter A1 - Tucci, Fabio A1 - Perrotta, Silverio A1 - Grammatico, Paola A1 - Hanenberg, Helmut A1 - Della Ragione, Fulvio A1 - Dufour, Carlo A1 - Savoia, Anna KW - Amino Acid Substitution KW - Cell Line KW - Cohort Studies KW - Computational Biology KW - Databases, Nucleic Acid KW - Fanconi Anemia KW - Fanconi Anemia Complementation Group Proteins KW - Founder Effect KW - Genotype KW - Humans KW - Italy KW - Mosaicism KW - Mutation KW - Polymorphism, Single Nucleotide AB -

Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes.

VL - 99 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24584348?dopt=Abstract ER -