title: Fanconi anemia: contribution of molecular analyses to the identification of bone marrow graft donors and the study of chimerism in grafted patients.
abstract: We report on the effectiveness of molecular studies regarding Fanconi anemia (FA) for a better selection of bone marrow graft donors and for post-transplant follow up. Ten unrelated FA patients and their families were analyzed by microsatellite markers. In 9 cases, the cytogenetic investigation of potential human leukocyte antigen (HLA)-identical related donors was normal, and the molecular analyses confirmed that they were also either normal or heterozygous carriers. For 1 patient, cytogenetic analysis of an HLA-identical sibling donor yielded ambiguous results with a relatively high number of chromosomal breakages using cross-linking agents. However, genotyping of this potential donor demonstrated his heterozygous state. Nine patients have received allogeneic bone marrow transplantation from HLA-matched related donors. Microsatellite analysis showed complete chimerism (CC) in all cases. The median follow up was 54 months (range 8-144 months). One patient out of 9 with CC rejected her graft without prior detection of a transitional mixed chimerism. Among these patients, 1 died 25 months after the transplantation of a chronic graft-versus-host-disease (GVHD). We conclude that, when the cytogenetic studies are not conclusive, molecular analyses are crucial to distinguish heterozygous carriers from asymptomatic FA Tunisian patients. Molecular analyses also allowed the evaluation of hematopoietic chimerism after allogeneic bone marrow transplantation and might be of value to identify patients with a high risk for graft rejection.
authors.affiliation: Laboratoire d'Immunologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, Tunisia.
authors.forename: Chiraz
authors.initials: C
authors.lastname: Bouchlaka
authors.forename: Tarek Ben
authors.initials: TB
authors.lastname: Othman
authors.forename: Lamia
authors.initials: L
authors.lastname: Aissaoui
authors.forename: Houda
authors.initials: H
authors.lastname: Elloumi
authors.forename: Moez
authors.initials: M
authors.lastname: Elloumi
authors.forename: Ahlem
authors.initials: A
authors.lastname: Amouri
authors.forename: Hela Ben
authors.initials: HB
authors.lastname: Abid
authors.forename: Sondes
authors.initials: S
authors.lastname: Hadiji
authors.forename: Hmida
authors.initials: H
authors.lastname: Slama
authors.forename: Hafedh
authors.initials: H
authors.lastname: Makni
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.forename: Koussay
authors.initials: K
authors.lastname: Dellagi
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D046528:Chimerism; D004268:DNA-Binding Proteins / Q000235:genetics; D005199:Fanconi Anemia / Q000235:genetics* / Q000601:surgery*; D052217:Fanconi Anemia Complementation Group A Protein; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D010375:Pedigree; D014019:Tissue Donors; D018183:Transplantation Chimera; D019737:Transplants
chemical_list: D004268:DNA-Binding Proteins; C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D005819:Genetic Markers; D006680:HLA Antigens