title: Cytogenetic and molecular study of 32 Down syndrome families: potential leukaemia predisposing role of the most proximal segment of chromosome 21q.
abstract: Down syndrome (DS) children have a 10-20-fold increased risk of developing ALL or AML compared to non-DS children. An increased disomic homozygosity of the polymorphic DNA markers in the pericentromeric region of chromosome 21q (21q11) has repeatedly been found in DS patients with ANLL-M7 and DS-specific transient abnormal myelopoiesis (TAM), compared to the majority of DS subjects without leukaemia. Analysis of cytogenetic heteromorphisms and 26 polymorphic DNA markers from chromosome 21q showed an increased number of pericentromeric crossovers between the non-disjoined chromosomes in DS-ANLL cases (3/11), compared to DS-ALL (0/9) and DS-nonleukaemic cases (0/12). These findings are compatible with the model of disomic homozygosity of the predisposing allele of a putative pericentromeric gene, as an explanation for the high prevalence of ANLL in DS.
authors.affiliation: Human Genetics Laboratory, Galliera Hospital, Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cavani
authors.forename: C
authors.initials: C
authors.lastname: Perfumo
authors.forename: A
authors.initials: A
authors.lastname: Argusti
authors.forename: M
authors.initials: M
authors.lastname: Pierluigi
authors.forename: L
authors.initials: L
authors.lastname: Perroni
authors.forename: K
authors.initials: K
authors.lastname: Schmiegelow
authors.forename: M B
authors.initials: MB
authors.lastname: Petersen
authors.forename: F E
authors.initials: FE
authors.lastname: Cotter
authors.forename: P
authors.initials: P
authors.lastname: Strigini
authors.forename: F
authors.initials: F
authors.lastname: Dagna-Bricarelli
authors.forename: D
authors.initials: D
authors.lastname: Nizetić
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004314:Down Syndrome / Q000150:complications / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000235:genetics*; D012307:Risk Factors