Parental origin and mechanisms of formation of cytogenetically recognisable de novo direct and inverted duplications

Cytogenetic, FISH, and molecular results of 20 cases with de novo tandem du plications of 18 different autosomal chromosome segments are reported. Ther e were 12 cases with direct duplications, three cases with inverted duplica tions, and five in whom determination of direction was not possible. In sev en cases a rearrangement between non-sister chromatids (N-SCR) was found, w hereas in the remaining 13 cases sister chromatids (SCR) were involved. Pat ernal. and maternal origin (7:7) was found almost equally in cases with SCR (3:4) and N-SCR (4:3). In the cases with proven inversion, there was mater nal and paternal origin in one case each. Twenty three out of 43 cytogeneti cally determined breakpoints correlated with common or rare fragile sites. In five cases, including all those with proven inverse orientation, all bre akpoints corresponded to common or rare fragile sites. In at least two case s, one with an interstitial duplication (dup(19)(q11q13)) and one with a te rminal duplication (dup(8) (p10p23)), concomitant deletions (del(8) (p23p23 .3) and del(19)(q13q13)) were found.