TY - JOUR
T1 - Spectrum of FANCA mutations in Italian Fanconi anemia patients
T2 - identification of six novel alleles and phenotypic characterization of the S858R variant.
AU - Savino, Maria
AU - Borriello, Adriana
AU - D'Apolito, Maria
AU - Criscuolo, Maria
AU - Del Vecchio, Maria
AU - Bianco, Anna Monica
AU - Di Perna, Michele
AU - Calzone, Rita
AU - Nobili, Bruno
AU - Zatterale, Adriana
AU - Zelante, Leopoldo
AU - Joenje, Hans
AU - Della Ragione, Fulvio
AU - Savoia, Anna
PY - 2003/10
Y1 - 2003/10
N2 - 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.
AB - 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.
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M3 - Article
C2 - 12955722
AN - SCOPUS:2142805258
VL - 22
SP - 338
EP - 339
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 4
ER -