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: Chiraz Bouchlaka, Tarek Ben Othman, Lamia Aissaoui, Houda Elloumi, Moez Elloumi, Ahlem Amouri, Hela Ben Abid, Sondes Hadiji, Hmida Slama, Hafedh Makni, Ali Saad, Sonia Abdelhak, Koussay Dellagi, Tunisian Fanconi Anemia Study Group
• Journal: Genetic testing (Genet Test) Vol. 8 Issue 3 Pg. 268-75 ( 2004) ISSN: 1090-6576 [Print] United States
• PMID: 15727250 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• FANCA protein, human
• Fanconi Anemia Complementation Group A Protein
• Genetic Markers
• HLA Antigens

Topics

• Adolescent
• Adult
• Bone Marrow Transplantation
• Child
• Chimerism
• DNA-Binding Proteins (genetics)
• Fanconi Anemia (genetics, surgery)
• Fanconi Anemia Complementation Group A Protein
• Female
• Genetic Markers (genetics)
• HLA Antigens (genetics)
• Haplotypes (genetics)
• Humans
• Male
• Microsatellite Repeats (genetics)
• Pedigree
• Tissue Donors
• Transplantation Chimera
• Transplants