Molecular analysis of Fanconi anemia

The experience of the bone marrow failure study group of the Italian Association of Pediatric Onco-Hematology

Daniela De Rocco, Roberta Bottega, Enrico Cappelli, Simona Cavani, Maria Criscuolo, Elena Nicchia, Fabio Corsolini, Chiara Greco, Adriana Borriello, Johanna Svahn, Marta Pillon, Cristina Mecucci, Gabriella Casazza, Federico Verzegnassi, Chiara Cugno, Anna Locasciulli, Piero Farruggia, Daniela Longoni, Ugo Ramenghi, Walter Barberi & 7 others Fabio Tucci, Silverio Perrotta, Paola Grammatico, Helmut Hanenberg, Fulvio Della Ragione, Carlo Dufour, Anna Savoia

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1022-1031
Number of pages10
JournalHaematologica
Volume99
Issue number6
DOIs
StatePublished - Jun 1 2014

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Fanconi Anemia
Hematology
Bone Marrow
Pediatrics
Mutation
Genes
Alleles
Pancytopenia
Frameshift Mutation
Genetic Heterogeneity
Nonsense Codon
Sequence Deletion
Missense Mutation
Neoplasms
Proteins

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

Molecular analysis of Fanconi anemia : The experience of the bone marrow failure study group of the Italian Association of Pediatric Onco-Hematology. / De Rocco, Daniela; Bottega, Roberta; Cappelli, Enrico; Cavani, Simona; Criscuolo, Maria; Nicchia, Elena; Corsolini, Fabio; Greco, Chiara; Borriello, Adriana; Svahn, Johanna; Pillon, Marta; Mecucci, Cristina; Casazza, Gabriella; Verzegnassi, Federico; Cugno, Chiara; Locasciulli, Anna; Farruggia, Piero; Longoni, Daniela; Ramenghi, Ugo; Barberi, Walter; Tucci, Fabio; Perrotta, Silverio; Grammatico, Paola; Hanenberg, Helmut; Ragione, Fulvio Della; Dufour, Carlo; Savoia, Anna.

In: Haematologica, Vol. 99, No. 6, 01.06.2014, p. 1022-1031.

Research output: Contribution to journalArticle

De Rocco, D, Bottega, R, Cappelli, E, Cavani, S, Criscuolo, M, Nicchia, E, Corsolini, F, Greco, C, Borriello, A, Svahn, J, Pillon, M, Mecucci, C, Casazza, G, Verzegnassi, F, Cugno, C, Locasciulli, A, Farruggia, P, Longoni, D, Ramenghi, U, Barberi, W, Tucci, F, Perrotta, S, Grammatico, P, Hanenberg, H, Ragione, FD, Dufour, C & Savoia, A 2014, 'Molecular analysis of Fanconi anemia: The experience of the bone marrow failure study group of the Italian Association of Pediatric Onco-Hematology', Haematologica, vol. 99, no. 6, pp. 1022-1031. https://doi.org/10.3324/haematol.2014.104224
De Rocco, Daniela ; Bottega, Roberta ; Cappelli, Enrico ; Cavani, Simona ; Criscuolo, Maria ; Nicchia, Elena ; Corsolini, Fabio ; Greco, Chiara ; Borriello, Adriana ; Svahn, Johanna ; Pillon, Marta ; Mecucci, Cristina ; Casazza, Gabriella ; Verzegnassi, Federico ; Cugno, Chiara ; Locasciulli, Anna ; Farruggia, Piero ; Longoni, Daniela ; Ramenghi, Ugo ; Barberi, Walter ; Tucci, Fabio ; Perrotta, Silverio ; Grammatico, Paola ; Hanenberg, Helmut ; Ragione, Fulvio Della ; Dufour, Carlo ; Savoia, Anna. / Molecular analysis of Fanconi anemia : The experience of the bone marrow failure study group of the Italian Association of Pediatric Onco-Hematology. In: Haematologica. 2014 ; Vol. 99, No. 6. pp. 1022-1031.
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AU - Cappelli, Enrico

AU - Cavani, Simona

AU - Criscuolo, Maria

AU - Nicchia, Elena

AU - Corsolini, Fabio

AU - Greco, Chiara

AU - Borriello, Adriana

AU - Svahn, Johanna

AU - Pillon, Marta

AU - Mecucci, Cristina

AU - Casazza, Gabriella

AU - Verzegnassi, Federico

AU - Cugno, Chiara

AU - Locasciulli, Anna

AU - Farruggia, Piero

AU - Longoni, Daniela

AU - Ramenghi, Ugo

AU - Barberi, Walter

AU - Tucci, Fabio

AU - Perrotta, Silverio

AU - Grammatico, Paola

AU - Hanenberg, Helmut

AU - Ragione, Fulvio Della

AU - Dufour, Carlo

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