A 11.7-Mb Paracentric Inversion in Chromosome 1q Detected in Prenatal Diagnosis Associated with Familial Intellectual Disability

Abstract

Most apparent balanced chromosomal inversions are usually clinically asymptomatic; however, infertility, miscarriages, and mental retardation have been reported in inversion carriers. We present a small family with a paracentric inversion 1q42.13q43 detected in routine prenatal diagnosis. Molecular cytogenetic methods defined the size of the inversion as 11.7 Mb and excluded other unbalanced chromosomal alterations in the patients. Our findings suggest that intellectual disability is caused by dysfunction, disruption, or position effects of genes located at or near the breakpoints involved in this inversion.

Familial Duplication/Deletion of 1q42.13q43 as Meiotic Consequence of an Intrachromosomal Insertion in Chromosome 1

“…They found 477 insertional translocations with an incidence of approximately 2.1%, demonstrating that the frequency detected with array-CGH seems to be higher . This result is confirmed by some other recent studies which estimated the frequency of these rearrangements at the submicroscopic level by array-CGH [Bartsch et al, 2001;Williams et al, 2009;Crepel et al, 2010;Rigola et al, 2015;Morris et al, 2016;Wang et al, 2016].…”

“…Chromosome 1q (mainly bands q42 to q43) has already been described to be involved in structural alterations, but only in 1 previous study [Rigola et al, 2015] and in both cases described in this paper the anomaly was precisely defined with molecular cytogenetic techniques. Most of the reported cases are the results of translocations involving the telomeric regions of chromosomes [Steffensen et al, 1977;Johnson et al, 1985;Watson et al, 1986;Kausch et al, 1988;Johnson, 1991;Ioan et al, 1992;Arai et al, 1994;Concolino et al, 1998;Fan et al, 1999;Bartsch et al, 2001;De Brasi et al, 2001;Gentile et al, 2003;Coccé et al, 2007;Hill et al, 2007;Tuschl et al, 2007;Chen et al, 2010Chen et al, , 2012Tartaglia et al, 2011;Khan et al, 2012;Morris et al, 2016].…”

“…Rearrangements of the region 1q42.13q43 are rare, with only 7 cases reported to date [Beemer et al, 1985;Bortotto et al, 1990;Kato et al, 2007;Williams et al, 2009;Crepel et al, 2010;Rigola et al, 2015;Wang et al, 2016]. The imbalances described are usually the result of inherited translocations involving other chromosomes, making difficult to establish a specific karyotype/phenotype correlation.…”

Study of comparative proteome between normal and inverted karyotypes of human mesenchymal stem cells

“…Most inversions have unique breakpoints and the inversion incidence in humans is rare, being estimated at 0.1-0.5 1,000 -1 in the population. Paracentric inversions have been described in all human chromosomes, but they are most common in chromosomes 1, 3, 5, 6, 7, 11, and 14 (Rigola et al, 2015).…”

“…However, infertility, spontaneous abortions and cognitive deficit have been reported in some patients with this type of inversion. On the other hand, cytogenetic molecular methods are necessary to detect or to rule out the presence of unbalanced chromosomal alterations, especially when dealing with MSC used in gene therapies (Rigola et al, 2015).…”