Intrachromosomal insertion mimicking a pericentric inversion: Molecular cytogenetic characterization of a three break rearrangement of chromosome 20

Abstract

Intrachromosomal insertions are uncommon rearrangements, in which a chromosomal segment is intercalated into another part of the same chromosome. The insertion may occur in the same arm (paracentric) or in the other arm (pericentric). The cytogenetic recognition of these structurally rearranged chromosomes can be difficult, and intrachromosomal insertions can be easily mistaken for inversions. We describe a case of a familial pericentric insertion of chromosome 20, initially misdiagnosed as a pericentric inversion in the healthy carrier and then reinterpreted as insertion in an abnormal child with a recombinant chromosome. Fluorescence in situ hybridization (FISH) allowed us to confirm the mechanism of recombinant formation and to locate the three breakpoints precisely. Our cytogenetically unbalanced epileptic patient carried a 20q deletion and 20p duplication, and the genes, CHRNA4 and KCNQ2 that have been implicated in autosomal dominant epilepsy, were deleted. The haplo-insufficiency of these two genes may contribute to the cause of epilepsy in patients with ring chromosome 20.

PGD for a carrier of an intrachromosomal insertion using aCGH

“…The common region duplicated in patients in whom Pierre Robin Sequence and flexion of the fingers have been observed is the 1q25 segment, which is involved in our patient [Aboura et al 2002]. Intrachromosomal insertions described in the literature have most commonly been detected in a child with congenital anomalies who has a recombinant chromosome [Ardalan et al 2005;Basinko et al 2008;Burnside et al 2009;Pramparo et al 2008;Wang et al 2010;Wilson et al 2012;Xanthopoulou et al 2010]. Other reported carriers of an intrachromosomal insertion have presented initially with a history of multiple miscarriages [Farrell and Chow 1992;Friedrich et al 2000], as in the patient presented here.…”

“…Balanced carriers of intrachromosomal insertions are phenotypically normal but are at increased risk for chromosomally unbalanced offspring due to crossing over during meiotic segregation [Madan and Menko 1992]. The size of the inserted segment determines the expected rate at which unbalanced gametes are generated [Ardalan et al 2005]. Figure 3 demonstrates possible recombinants as a result of crossing over events involving the inserted segment.…”

“…Cytogenetic recognition of intrachromosomal insertions is difficult as these can easily be mistaken for inversions or translocations [Ardalan et al 2005;Collinson et al 2004;Madan and Menko 1992;Madan and Nieuwint 2002]. Correct identification of an insertion is important because the risk of a liveborn child with a recombinant chromosome arising from a paracentric inversion carried by one of the parents is negligible [Gardner and Sutherland 1996] but there is a much higher risk of recombinants for carriers of intrachromosomal insertions [Daniel et al 1988;Madan and Menko 1992].…”

“…Correct identification of an insertion is important because the risk of a liveborn child with a recombinant chromosome arising from a paracentric inversion carried by one of the parents is negligible [Gardner and Sutherland 1996] but there is a much higher risk of recombinants for carriers of intrachromosomal insertions [Daniel et al 1988;Madan and Menko 1992]. As a result of the difficulty in identifying intrachromosomal insertions by conventional cytogenetics, this condition is likely underestimated [Ardalan et al 2005].…”

Partial Trisomy 2p and Partial Monosomy 2q Arising from a Paternal Intrachromosomal 2q-into-2p Between-Arm Insertion and Paracentric Inversion: Molecular Cytogenetic Characterization of a Four-Break Rearrangement

“…Most of these features have previously been described in individuals with interstitial deletion of 2q14.1. Copyright © 2013 S. Karger AG, Basel Intrachromosomal insertions are uncommon rearrangements and the cytogenetic recognition of these structurally rearranged chromosomes can be difficult and easily mistaken for inversions [Madan and Menko, 1992;Henry et al, 1993; Gardner and Sutherland, 2004;Ardalan et al, 2005]. Around 40 cases of intrachromosomal insertions have been published so far [Madan and Menko, 1992;Henry et al, 1993;Barber et al, 1994; TuckMuller et al, 1996;Goss et al, 1998;Park et al, 1998;Friedrich et al, 2000;Starke et al, 2001;Engelen et al, 2003;Collinson et al, 2004;Ardalan et al, 2005;Lybaek et al, 2009;Wang et al, 2010].…”