title: Molecular characterization of three novel Fanconi anemia mutations in Israeli Arabs.
abstract: OBJECTIVE
  In a previous study, we investigated the molecular basis of Fanconi anemia (FA) in 13 unrelated Israeli Jewish FA patients and identified four ethnicity specific mutations. In the present study we extended our study to Israeli Arab patients.
  
  
  METHODS
  We studied three consanguineous families with nine FA patients and an additional unrelated patient. DNA single-strand conformation polymorphism of each exon of the FANCA and FANCG genes was followed by sequence analysis of the aberrantly migrating fragments and by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of the splice-site mutations identified.
  
  
  RESULTS
  Three unique disease-causing mutations were identified: (i) FANCA gross deletion of exons 6-31; (ii) FANCA splice-site mutation IVS 42-2A>C; (iii) FANCG splice-site mutation IVS4+3A>G. Sequence analysis of the FANCA gross deletion revealed recombination between two highly homologous Alu elements. cDNA analysis of the two splice mutations suggested intron 42 retention in FANCA IVS 42-2A>C and exon 4 skipping in FANCG IVS4+3A>G. The clinical condition of eight patients with FANCA mutations was severe.
  
  
  CONCLUSIONS
  Two unique FANCA mutations and one FANCG mutation were identified in Israeli Arab FA patients. Deletion of FANCA exon 6-31 as in previously described gross deletions was within introns rich in Alu repeats. To the best of our knowledge, the FANCA IVS 42-2A>C mutation is the first in this gene to result in intron retention. Further analysis of FA mutations will enable prenatal diagnosis and a rational therapeutic approach including frequent monitoring and early bone marrow transplantation.
authors.affiliation: Pediatric Hematology Laboratory, Felsenstein Research Center, Beilinson Campus, Petah Tiqva, Israel. htamary@post.tau.ac.il
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
authors.forename: Orly
authors.initials: O
authors.lastname: Dgany
authors.forename: Helen
authors.initials: H
authors.lastname: Toledano
authors.forename: Zvi
authors.initials: Z
authors.lastname: Shalev
authors.forename: Tatyana
authors.initials: T
authors.lastname: Krasnov
authors.forename: Lea
authors.initials: L
authors.lastname: Shalmon
authors.forename: Tali
authors.initials: T
authors.lastname: Schechter
authors.forename: Dani
authors.initials: D
authors.lastname: Bercovich
authors.forename: Dina
authors.initials: D
authors.lastname: Attias
authors.forename: Ruth
authors.initials: R
authors.lastname: Laor
authors.forename: Ariel
authors.initials: A
authors.lastname: Koren
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D020087:Alu Elements / Q000235:genetics; D018912:Arabs / Q000235:genetics*; D002648:Child; D003241:Consanguinity; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005199:Fanconi Anemia / Q000208:ethnology / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein; D052241:Fanconi Anemia Complementation Group G Protein; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D007557:Israel; D008297:Male; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C498471:FANCA protein, human; C499909:FANCG protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D052241:Fanconi Anemia Complementation Group G Protein; D011506:Proteins; D022821:RNA Splice Sites