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

Abstract

Rearrangements of the region 1q42.13q43 are rare, with only 7 cases reported to date. The imbalances described are usually the result of inherited translocations with other chromosomes. Moreover, few cases of both inter- and intrachromosomal deletions/duplications detected cytogenetically have been described. We report the molecular cytogenetic characterization of an inverted insertion involving the region 1q42.13q43 and segregating in 2 generations of a family. The deletion and the duplication of the same segment were detected in 2 affected family members. SNP array analysis showed the familial origin of the deletion/duplication due to the occurrence of a crossing-over during meiosis. Our report underlines the importance of determining the correct origin of chromosomal aberrations using different molecular cytogenetic tests in order to provide a good estimation of the reproductive risk for the members of the family.

An Apparently Balanced Complex Chromosome Rearrangement Involving Seven Breaks and Four Chromosomes in a Healthy Female and Segregation/Recombination in Her Affected Son

“…A search of the literature using the PubMed database and the keywords "duplication 4p" OR "trisomy 4p" OR "syndrome 4p" OR "duplication 1q" OR "trisomy 1q" OR "syndrome 1q" OR "complex chromosomal rearrangements", and a search of the Genome Browser database and the DECIPHER platform, found no case with the same set of alterations. However, recombinants with duplications or deletions arising from intra-chromosomal insertions as a result of a crossover in the interstitial or the inserted segment have been well documented for most chromosomes, including chromosome 1 [Madan and Menko, 1992;Jones et al, 2014;Silipgni et al, 2017]. The clinical features are summarized in Table 1.…”

“…However, the clinical phenotype of trisomy 1q (q42qter) in cases involving another chromosome is not properly defined in the literature. Moreover, intrachromosomal insertions are rare phenomena, characterized by the presence of 3 breakpoints and the repositioning of a chromosome segment into another location in the same chromosome [Silipgni et al, 2017], that lead to imbalances, such as deletions or duplications, resulting from recombination within the inserted segment [Nowakowska et al, 2012].…”

Language impairment with a microduplication in 1q42.3q43

“…Subjects with duplications suffer from language deficits. Specifically, the child examined by Silipigni et al (2017) showed cognitive and social delay, and said his first words at the age of 2 only. Nonetheless, a detailed characterization of the language problems exhibited by patients with duplications of the distal region of the long arm of chromosome 1 is still pending.…”

<italic>CHRM3</italic>基因与孤独症谱系障碍

“…, (Happe, Ronald, & Plomin, 2006), 一些 针对刻板行为和交流障碍的研究已证实了该现象 (Cuccaro et al, 2003;Buxbaum et al, 2001)。所以 Thiel, Driver, & Dolan, 2003;Dani & Bertrand, 2007;Karva & Kimchi, 2014), 胆碱能信号通路异 常与多种精神类疾病的发生有关 (Bowen, Smith, White, & Davison, 1976;Whitehouse et al, 1982; Deng, & Reiner., 2016)。动物模型研究发现胆碱能 Perry et al, 2001;Lee et al, 2002;Martin-Ruiz et al, 2004;Ray et al, 2005;Friedman et al, 2006;Deutsch, Urbano, Neumann, Burket, & Katz, 2010;Petersen et al, 2013) Perrone et al, 2012;Petersen et al, 2013;Soueid et al, 2016)。该基因突变患者会表现出不 同程度的行为异常、认知障碍、言语障碍以及运 动发育迟缓等问题 (Silipigni et al, 2017;Luukkonen et al, 2017) 6(17), 1−8 Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995). Autism as a strongly genetic disorder: Evidence from a British twin study.…”