Spectrum of FANCA mutations in Italian Fanconi anemia patients: identification of six novel alleles and phenotypic characterization of the S858R variant.

Maria Savino, Adriana Borriello, Maria D'Apolito, Maria Criscuolo, Maria Del Vecchio, Anna Monica Bianco, Michele Di Perna, Rita Calzone, Bruno Nobili, Adriana Zatterale, Leopoldo Zelante, Hans Joenje, Fulvio Della Ragione, Anna Savoia

Research output: Contribution to journalArticlepeer-review

Abstract

Fanconi anemia (FA) is an autosomal recessive disorder characterized by genomic instability, bone marrow failure, congenital malformations, and cancer predisposition. FA is a genetically heterogeneous disease with at least seven genes so far identified. The role of FA proteins is unknown although they interact in a common functional pathway. Here, we report six novel FANCA sequence changes and review all the mutations identified in Italy. Except for two missense substitutions, all are expected to cause a premature termination of the FANCA protein at various sites throughout the molecule. The premature terminations are due to nonsense and splice site mutations, as well as small insertions and deletions, and large genomic rearrangements. The expected truncated proteins were not detectable on Western blot analyses. The FANCA-S858R variant is instead expressed at lower level than that seen in normal cell lines and is associated with a non-ubiquinated FANCD2 protein, strongly suggesting that the amino acid substitution is a disease-causing mutation. The spectrum of FA mutations is widely in agreement with the heterogeneous ethnic origin of the Italian population.

Original languageEnglish
Pages (from-to)338-339
Number of pages2
JournalHuman Mutation
Volume22
Issue number4
Publication statusPublished - Oct 2003

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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