title: Familial myelodysplastic syndromes, monosomy 7/trisomy 8, and mutator effects.
abstract: A family is reported, in which two sisters presented with myelodysplastic syndrome (MDS), namely refractory anemia with excess of blasts in transformation (RAEB-t), and refractory anemia (RA). Bone marrow chromosome changes were present in both: trisomy and tetrasomy 8 (with a pericentric inversion of one chromosome 8) in the older sister, and monosomy 7 (with clones with additional trisomies 19 and 21) in the younger one. Molecular data were obtained on the parental chromosome involved in these numerical anomalies, which proved to be of paternal origin in these cases. The observations of this family, and a review of familial cases of MDS/acute myeloid leukemia (AML), led us to consider that they may be divided into two groups: those which arise on the basis of a Mendelian predisposing disorder exerting a mutator effect, often with the acquisition of monosomy 7, and those in which no specific Mendelian predisposing disease is recognized, as the familial monosomy 7 cases and the one reported here. We postulate that in these families an inherited mutator effect is present and that it causes a karyotype instability, which leads to MDS/AML, often through the acquisition of monosomy 7 and trisomy 8.
authors.affiliation: Sezione di Biologia e Genetica, Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università dell'Insubria, Via J.H. Dunant 5, 21100 Varese, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maserati
authors.forename: Antonella
authors.initials: A
authors.lastname: Minelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Menna
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Cecchini
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Rossi
authors.forename: Paola
authors.initials: P
authors.lastname: De Filippi
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Curto
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasquali
mesh_terms: D000293:Adolescent; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics*; D002648:Child; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006801:Humans; D009006:Monosomy; D014314:Trisomy