Duplication of 9 p11.2‐p13.1: a benign cytogenetic variant

Abstract

The detection of very rare variants in prenatal diagnosis often causes counseling difficulties and anxiety in parents. We describe a duplication of the proximal region of chromosome 9 short arm in two cases of prenatal diagnosis and in one young woman, with evidence that such rearrangement is an uncommon variant. The duplication was investigated using Fluorescence in situ hybridization (FISH). Although the cytogenetic findings were indicative of a 'duplication 9p syndrome' associated with mental and developmental retardation, we were able to demonstrate that the rearrangement was a heteromorphism with no phenotypic consequence. We also determined the breakpoint regions of the rearrangement and identified the BAC probes that precisely define the duplicated region devoid of risk of phenotypic effects.

Novel deletion variants of 9q13–q21.12 and classical euchromatic variants of 9q12/qh involve deletion, duplication and triplication of large tracts of segmentally duplicated pericentromeric euchromatin

“…This is in contrast to the situation on chromosome 16, where duplications of unique sequence proximal 16q are found within the major heterochromatic block and are associated with developmental delay and behavioural problems. 24 Finally, we have confirmed the nature and extent of the duplications that underlie the 9p12 euchromatic variants of chromosome 9 which extend over the same area identified by Di Giacomo et al 10 It is interesting that the 9p12 amplification variants reported by Lecce et al 11 involve clones at both ends of the 9p12 duplication variant region ( Table 1). The pericentromeric region of chromosome 9 is thought to follow the 'domain' model established for chromosome 10 in which the centromere is surrounded by large alphoid repeat arrays which are themselves flanked by interchromosomally duplicated sequences which are, in turn, flanked by intrachromosomal duplications 25 .…”

Rare structural chromosomal abnormalities in prenatal diagnosis; clinical and cytogenetic findings on 10125 prenatal cases

“…Genetic counseling was given to parents according to the literature and the family decided to continue the pregnancy that resulted in normal pregnancy outcome. Duplications of chromosome 9p11.2-p13.1 and 9q13-q21.12 have been previously reported as uncommon euchromatin variants that are associated with a normal phenotype (22). In both of our cases the pregnancies were continued to term and the babies were born without any clinical abnormality.…”

Another Family with a Euchromatic Duplication Variant of 9q13-q21.1 Derived from Segmentally Duplicated Pericentromeric Euchromatin

“…This duplication EV of 9q13-q21.1 is not believed to have any phenotypic or reproductive consequences because (1) the mother was phenotypically normal; (2) the pregnancy resulted in a healthy newborn at term; (3) extra G-dark bands in proximal 9q have been previously reported as heteromorphisms [Jalal et al, 1990;Knight et al, 1993;Reddy, 1996]; (4) other euchromatic deletion, duplication, triplication, and amplification variants of this SD region have not yet been associated with any consistent phenotypic or reproductive consequences [Wojiski et al, 1997;Di Giacomo et al, 2004;Lecce et al, 2006;Willatt et al, 2007;Barber, 2010;Cho et al, 2011;JosephGeorge et al, 2011], and (5) the material involved is known to be made up of multiple smaller CNVs [Redon et al, 2006]. We assume that the smaller pericentromerichotspot CNVs found in both control and affected populations [Itsara et al, 2009] are a reflection of their frequency rather than variable pathogenicity.…”

“…Most other EVs of chromosome 9 have been shown to be derived from segmental duplications (SDs) that flank 9qh/q12 in humans [Wojiski et al, 1997;Starke et al, 2002;Di Giacomo et al, 2004;Lecce et al, 2006;Willatt et al, 2007] and, recently, Joseph-George et al [2011] found 3-4 additional copies of an SD cassette in 2 families with 9q13-q21 duplication EVs. In contrast, Cho et al [2011] reported microscopically similar variants of 9q13 as heterochromatic heteromorphisms.…”