title: Clinical aspects of Fanconi anemia individuals with the same mutation of FANCF identified by next generation sequencing.
abstract: BACKGROUND
  Fanconi anemia (FA) is a rare genetic disease characterized by congenital malformations, aplastic anemia and increased risk of developing malignancies. FA is genetically heterogeneous as it is caused by at least 17 different genes. Among these, FANCA, FANCC, and FANCG account for approximately 85% of the patients whereas the remaining genes are mutated in only a small percentage of cases. For this reason, the molecular diagnostic process is complex and not always extended to all the FA genes, preventing the characterization of individuals belonging to rare groups.
  
  
  METHODS
  The FA genes were analyzed using a next generation sequencing approach in two unrelated families.
  
  
  RESULTS
  The analysis identified the same, c.484_485del, homozygous mutation of FANCF in both families. A careful examination of three electively aborted fetuses in one family and one affected girl in the other indicated an association of the FANCF loss-of-function mutation with a severe phenotype characterized by multiple malformations.
  
  
  CONCLUSIONS
  The systematic use of next generation sequencing will allow the recognition of individuals from rare complementation groups, a better definition of their clinical phenotypes, and consequently, an appropriate genetic counseling.
authors.affiliation: Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Nicchia
authors.affiliation: Genetic Counseling Service, Department of Pediatrics, Regional Hospital of Bolzano, Bolzano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedicenti
authors.affiliation: Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: De Rocco
authors.affiliation: Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Greco
authors.affiliation: Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bottega
authors.affiliation: Genetic Counseling Service, Department of Pediatrics, Regional Hospital of Bolzano, Bolzano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Inzana
authors.affiliation: Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Faleschini
authors.affiliation: Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bonin
authors.affiliation: Clinical and Experimental Hematology Unit, G. Gaslini Children's Hospital, Genoa, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cappelli
authors.affiliation: Human Genetics Laboratory "E.O. Ospedali Galliera", Genoa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mogni
authors.affiliation: Genetic Counseling Service, Department of Pediatrics, Regional Hospital of Bolzano, Bolzano, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Stanzial
authors.affiliation: Clinical and Experimental Hematology Unit, G. Gaslini Children's Hospital, Genoa, Italy.
authors.forename: Johanna
authors.initials: J
authors.lastname: Svahn
authors.affiliation: Clinical and Experimental Hematology Unit, G. Gaslini Children's Hospital, Genoa, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.affiliation: Department of Medical Sciences, University of Trieste, Trieste, Italy.|Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
mesh_terms: D002675:Child, Preschool; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree
keywords: FANCF; Fanconi anemia; VACTERL-H association; genetic heterogeneity; next generation sequencing