Chromosome fragility in patients with Fanconi anaemia: diagnostic implications and clinical impact.
J Med Genet
; 48(4): 242-50, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21217111
ABSTRACT
BACKGROUND:
Fanconi anaemia (FA) is a rare syndrome characterized by bone marrow failure, malformations and cancer predisposition. Chromosome fragility induced by DNA interstrand crosslink (ICL)-inducing agents such as diepoxybutane (DEB) or mitomycin C (MMC) is the 'gold standard' test for the diagnosis of FA.OBJECTIVE:
To study the variability, the diagnostic implications and the clinical impact of chromosome fragility in FA.METHODS:
Data are presented from 198 DEB-induced chromosome fragility tests in patients with and without FA where information on genetic subtype, cell sensitivity to MMC and clinical data were available.RESULTS:
This large series allowed quantification of the variability and the level of overlap in ICL sensitivity among patients with FA and the normal population. A new chromosome fragility index is proposed that provides a cut-off diagnostic level to unambiguously distinguish patients with FA, including mosaics, from non-FA individuals. Spontaneous chromosome fragility and its correlation with DEB-induced fragility was also analysed, indicating that although both variables are correlated, 54% of patients with FA do not have spontaneous fragility. The data reveal a correlation between malformations and sensitivity to ICL-inducing agents. This correlation was also statistically significant when the analysis was restricted to patients from the FA-A complementation group. Finally, chromosome fragility does not correlate with the age of onset of haematological disease.CONCLUSIONS:
This study proposes a new chromosome fragility index and suggests that genome instability during embryo development may be related to malformations in FA, while DEB-induced chromosome breaks in T cells have no prognostic value for the haematological disease.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Prevencao_e_fatores_de_risco
/
Hereditariedade
Base de dados:
MEDLINE
Assunto principal:
Fragilidade Cromossômica
/
Anemia de Fanconi
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Espanha