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Chromoanagenesis is a cellular mechanism that leads to complex chromosomal rearrangements (CCR) during a single catastrophic event. It may result in loss and/or gain of genetic material and may be responsible for various phenotypes. These rearrangements are usually sporadic. However, some familial cases have been reported. Here, we studied six families in whom an asymptomatic or paucisymptomatic parent transmitted a CCR to its offspring in an unbalanced manner. The rearrangements were characterized by karyotyping, fluorescent in situ hybridization, chromosomal microarray (CMA) and/or whole genome sequencing (WGS) in the carrier parents and offspring. We then hypothesized meiosis-pairing figures between normal and abnormal parental chromosomes that may have led to the formation of new unbalanced rearrangements through meiotic recombination. Our work indicates that chromoanagenesis might be associated with a normal phenotype and normal fertility, even in males, and that WGS may be the only way to identify these events when there is no imbalance. Subsequently, the CCR can be transmitted to the next generation in an unbalanced and unpredictable manner following meiotic recombination. Thereby, prenatal diagnosis using CMA should be proposed to these families to detect any pathogenic imbalances in the offspring., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report on a prenatally diagnosed unusual case of inverted terminal duplication of the short arm of chromosome 2, leading to interstitial telomeric sequences (ITSs) and partial trisomy 2p. To our knowledge, there are only 4 further cases of pure partial trisomy 2p reported prenatally. Here, the mother was referred at 22 weeks of gestation for isolated fetal congenital heart malformation at ultrasound. The karyotype of amniotic fluid cells displayed a large duplication of the short arm of chromosome 2 that was further investigated by array-CGH, which detected a 1-copy gain of 43.75 Mb in chromosome 2 at 2p21p25.3. FISH confirmed the presence of an inverted duplication in the short arm of chromosome 2 involving the region 2p21pter and revealed the presence of ITSs at the breakpoint in chromosome 2p21. This report contributes to the prenatal description of the syndrome. We also discuss the possible mechanisms leading to this duplication and the formation of ITSs which are rarely described in constitutional rearrangements., (© 2017 S. Karger AG, Basel.)

We report a prenatally diagnosed case of partial trisomy 2p and partial monosomy 3p, resulting from unbalanced translocation (2;3)(p25.1;p25.3) of paternal origin. Parents were non consanguineous Caucasians, with familial history of recurrent miscarriages on the father's side. Detailed sonographic examination of the fetus showed a septated cystic hygroma measuring 6 mm at 13 weeks' gestation. Karyotyping and fluorescent in situ hybridization (FISH) analysis of cultured amniotic fluid cells revealed an unbalanced translocation der(3)t(2;3)(p25.1; p25.3) and apparently balanced inv(3)(p13p25.3) in a fetus. Parental cytogenetic evaluation using karyotyping and FISH analysis showed the presence of both a balanced translocation and a paracentric inversion in father t(2;3) (p25.1;p25.3) inv(3)(p13p25.3). Microarray analysis showed a 11.6 Mb deletion at 3p26.3-p25.3 and duplication of 10.5 Mb at the 2p25.3-p25 region. The duplicated region at 2p25.1p25.3 contains 45 different genes, where 12 are reported as OMIM morbid genes with different phenotypical implications. The deleted region at 3p26.3-p25.3 contains 65 genes, out of which 27 are OMIM genes. Three of these (CNTN4, SETD5 and VHL) were curated by Clingene Dosage Gene Map and were given a high haplo-insufficiency score. Genes affected by the unbalanced translocation could have contributed to some specific phenotypic changes of the fetus in late pregnancy. The application of different cytogenetic methods was essential in our case, allowing the detection of different types of structural chromosomal aberrations and more thorough genetic counseling for future pregnancies. [ABSTRACT FROM AUTHOR]

Tandem DNA repeats derived from the ancestral (TTAGGG)n run were first detected at chromosome ends of the majority of living organisms, hence the name telomeric DNA repeats. Subsequently, it has become clear that telomeric motifs are also present within chromosomes, and they were suitably called interstitial telomeric sequences (ITSs). It is well known that telomeric DNA repeats play a key role in chromosome stability, preventing end-to-end fusions and precluding the recurrent DNA loss during replication. Recent data suggest that ITSs are also important genomic elements as they confer its karyotype plasticity. In fact, ITSs appeared to be among the most unstable microsatellite sequences as they are highly length polymorphic and can trigger chromosomal fragility and gross chromosomal rearrangements. Importantly, mechanisms responsible for their instability appear to be similar to the mechanisms that maintain the length of genuine telomeres. This review compares the mechanisms of maintenance and dynamic properties of telomeric repeats and ITSs and discusses the implications of these dynamics on genome stability. [ABSTRACT FROM AUTHOR]