Familial myelodysplastic syndromes, monosomy 7/trisomy 8, and mutator effects.
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.
Maserati
Emanuela
E
Sezione di Biologia e Genetica, Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università dell'Insubria, Via J.H. Dunant 5, 21100 Varese, Italy.
Minelli
Antonella
A
Menna
Giuseppe
G
Cecchini
Maria Paola
MP
Bernardo
Maria Ester
ME
Rossi
Gabriele
G
De Filippi
Paola
P
Lo Curto
Francesco
F
Danesino
Cesare
C
Locatelli
Franco
F
Pasquali
Francesco
F
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