@article {3549, title = {Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology.}, journal = {Haematologica}, volume = {99}, year = {2014}, month = {2014 Jun}, pages = {1022-31}, abstract = {

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.

}, keywords = {Amino Acid Substitution, Cell Line, Cohort Studies, Computational Biology, Databases, Nucleic Acid, Fanconi Anemia, Fanconi Anemia Complementation Group Proteins, Founder Effect, Genotype, Humans, Italy, Mosaicism, Mutation, Polymorphism, Single Nucleotide}, issn = {1592-8721}, doi = {10.3324/haematol.2014.104224}, author = {De Rocco, Daniela and Bottega, Roberta and Cappelli, Enrico and Cavani, Simona and Criscuolo, Maria and Nicchia, Elena and Corsolini, Fabio and Greco, Chiara and Borriello, Adriana and Svahn, Johanna and Pillon, Marta and Mecucci, Cristina and Casazza, Gabriella and Verzegnassi, Federico and Cugno, Chiara and Locasciulli, Anna and Farruggia, Piero and Longoni, Daniela and Ramenghi, Ugo and Barberi, Walter and Tucci, Fabio and Perrotta, Silverio and Grammatico, Paola and Hanenberg, Helmut and Della Ragione, Fulvio and Dufour, Carlo and Savoia, Anna} }