Parental age, and how extra isochromosomes (secondary trisomy) arise

Dyke, Daniel L. Van; Babu, V. Ramesh; Weiss, Lester

doi:10.1111/j.1399-0004.1987.tb03328.x

Cited by 36 publications

(1 citation statement)

References 21 publications

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“…A proportion of the latter are heterodisomic and thus represent real Robertsonian translocations with two long arms from different chromosome 21, while the majority are isodisomic with two identical long arms of chromosome 21 constituting an isochromosome 21 (i(21q)) [ 8 , 9 , 10 ]. Different mechanisms have been proposed for the formation of isochromosomes, including a mis-division of the centromere and a U-type exchange between sister chromatids [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report

2021

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Background Fetoplacental discrepancies occur in approximately 1–2% of analyzed prenatal cases. They are typically due to confined placental mosaicism, where an aberration is observed in the placental cells but not found in the fetal cells. Confined placental mosaicism usually involves aneuploidies and more sparsely structural chromosomal aberrations. To the best of our knowledge, this is the first reported case of a discrepancy in the analyses of chorionic villus sampling and amniocentesis involving two different structural chromosomal aberrations of chromosome 21. Case presentation We report a 33-year-old woman who was referred for a non-invasive prenatal testing due to an increased risk of trisomy 21 gleaned from a combined ultrasound and blood test. The non-invasive prenatal testing showed an increased risk of trisomy 21 with a normalized coverage signal that did not match the fetal cell-free DNA fraction. Rapid aneuploidy detection performed on uncultured chorionic villi indicated mosaicism for trisomy 21. The follow-up analyses revealed discordant chromosomal aberrations: 46,XY,der(21)t(10;21)(p11.21;q10) in the analysis of the chorionic villus sampling and 46,XY, + 21,der(21;21)(q10;q10) in the analysis of the amniocentesis. Thus, the analyses indicated mosaicism for a cell line containing trisomy 21 and a cell line containing a partially duplicated short arm of chromosome 10 in the chorionic villi and complete trisomy 21 resulting from an isochromosome 21 in the amniotic fluid. The analyses of the lymphocytes and the fibroblasts of the woman were normal. Conclusions We propose a multiple-step mechanism as a possible theoretical explanation for the formation of these discordant structural chromosomal aberrations in the chorionic villi and amniotic fluid. With this case report, we want to highlight the importance of understanding the possible underlying embryological mechanisms when interpreting results from different prenatal analyses.

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Section: Introductionmentioning

confidence: 99%

Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report

2021

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Report of two new cases of Pallister-Killian syndrome confirmed by FISH: Tissue-specific mosaicism and loss of i(12p) by in vitro selection

Schubert¹,

Viersbach²,

Eggermann³

et al. 1997

Am. J. Med. Genet.

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Tissue-specific mosaic distribution of an additional isochromosome 12p is the characteristic chromosomal aberration in Pallister-Killian syndrome. Often it is confined to fibroblasts, whereas lymphocytes show a normal karyotype. Two cases are reported in which the distribution of the additional i(12p) was analysed in various tissues. The isochromosomes were characterised by conventional banding technics and fluorescence in situ hybridization (FISH). In the first case, diagnosed prenatally, 4 different tissues were analysed. A direct preparation of chorionic villi (21 gestational weeks) showed an extra marker chromosome in 19% and two additional copies in 3% of the examined cells. In two cultures of amniocytes (17 and 21 weeks), the i(12p) was observed in 23% and 12%, respectively. It was absent in cultured lymphocytes of fetal blood (21 weeks). The fibroblast long-term culture of umbilical cord showed the i(12p) in 100% of metaphases. In the second case of a term infant the i(12p) was diagnosed in cultured lymphocytes (4%) and fibroblasts (93%). Secondary loss of the isochromosome was evaluated by in vitro selection in case 2 analysing metaphases and interphases of fibroblasts in the 1st, 4th and 5th subculture using FISH. The proportion of cells with i(12p) decreased from 93% to 40% and to 28%, respectively. DNA analysis in case 1 showed a maternal meiotic origin of the i(12p). The prenatally detected clinical findings in both cases showed characteristic abnormalities of the Pallister-Killian syndrome.

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Molecular analysis of mosaicism for two different de novo acrocentric rearrangements demonstrates diversity in Robertsonian translocation formation

et al. 1998

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Robertsonian translocations (ROBs) involving chromosome 21 occur in about 5% of individuals with Down syndrome. ROBs are the most common chromosomal rearrangements in humans and are formed through whole arm exchanges of any two acrocentric chromosomes. The de novo formation of ROBs occurs at exceptionally high rates. The present case concerns a child with mosaic Down syndrome who has two cell lines that contain two different de novo ROBs: 45,XX,rob(14;21)(q10;q10) and 46,XX,rea(21;21)(q10;q10),+21. To elucidate the mechanisms by which the rearrangements formed, somatic cell hybrids were constructed to allow the parental origins of the chromosomes involved in the ROBs to be distinguished. The analysis of the hybrids showed that the rob(14q21q) must have formed postzygotically because it contained a maternal chromosome 14 and a paternal chromosome 21. Furthermore, hybrid analysis of the rea(21q21q) demonstrated two copies of the same chromosome from the mother and thus, by definition, was an isochromosome [i(21q)]. All free-lying chromosomes 21 isolated in hybrids were of maternal origin. These chromosomes may have originated from either of the patient's cell lines. We present four hypotheses for the formation of the two cell lines of this child. This case is part of an ongoing project to determine the mechanism(s) of de novo ROB formation and the results differ from the other de novo rob(14q21q) studied in our laboratory (n = 7) in that all previously studied translocations were maternally derived, leading to the conclusion that most de novo rob(14q21q) occur in oogenesis. The current case illustrates that other mechanisms may contribute to ROB formation.

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Parental age, and how extra isochromosomes (secondary trisomy) arise

Cited by 36 publications

References 21 publications

Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report

Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report

Report of two new cases of Pallister-Killian syndrome confirmed by FISH: Tissue-specific mosaicism and loss of i(12p) by in vitro selection

Molecular analysis of mosaicism for two different de novo acrocentric rearrangements demonstrates diversity in Robertsonian translocation formation

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