Trisomy First, Translocation Second, Uniparental Disomy and Partial Trisomy Third: A New Mechanism for Complex Chromosomal Aneuploidy

Schinzel, Albert; Kotzot, Dieter; Brecevic, Lukrecija; Robinson, Wendy P.; Dutly, Fabrizio; Dauwerse, Hans G.; Binkert, Franz; Baumer, Alessandra; Ausserer, Bernd

doi:10.1159/000484782

Cited by 33 publications

(19 citation statements)

References 8 publications

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“…Maternal UPD(16) has been reported in a boy with various dysmorphic features, developmental delay, and partial trisomy 16p mosaicism only 88. In this case, formation by trisomy first, translocation second, and uniparental disomy and partial trisomy third was inferred.…”

Section: Reviewmentioning

confidence: 71%

Complex and segmental uniparental disomy (UPD): review and lessons from rare chromosomal complements

Kotzot¹

2001

Journal of Medical Genetics

123

107

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Objective-To review all cases with segmental and/or complex uniparental disomy (UPD), to study aetiology and mechanisms of formation, and to draw conclusions. Design-Searching published reports in Medline.Results-The survey found at least nine cases with segmental UPD and a normal karyotype, 22 cases with UPD of a whole chromosome and a simple or a nonhomologous Robertsonian translocation, eight cases with UPD and two isochromosomes, one of the short arm and one of the long arm of a non-acrocentric chromosome, 39 cases with UPD and an isochromosome of the long arm of two homologous acrocentric chromosomes, one case of UPD and an isochromosome 8 associated with a homozygous del(8)(p23.3pter), and 21 cases with UPD of a whole or parts of a chromosome associated with a complex karyotype. Segmental UPD is formed by somatic recombination (isodisomy) or by trisomy rescue. In the latter mechanism, a meiosis I error is associated with meiotic recombination and an additional somatic exchange between two non-uniparental chromatids. Subsequently, the chromatid that originated from the disomic gamete is lost (iso-and heterodisomy). In cases of UPD associated with one isochromosome of the short arm and one isochromosome of the long arm of a non-acrocentric chromosome and in cases of UPD associated with a true isochromosome of an acrocentric chromosome, mitotic complementation is assumed. This term describes the formation by misdivision at the centromere during an early mitosis of a monosomic zygote. In cases of UPD associated with an additional marker chromosome, either mitotic formation of the marker chromosome in a trisomic zygote or fertilisation of a gamete with a marker chromosome formed in meiosis by a disomic gamete or by a normal gamete and subsequent duplication are possible. Conclusions-Research in the field of segmental and/or complex UPD may help to explain undiagnosed non-Mendelian disorders, to recognise hotspots for meiotic and mitotic recombinations, and to show that chromosomal segregation is more complex than previously thought. It may also be helpful to map autosomal recessively inherited genes, genes/regions of genomic imprinting, and dysmorphic phenotypes. Last but not least it would improve genetic counselling. (J Med Genet 2001;38:497-507)

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Section: Reviewmentioning

confidence: 71%

Complex and segmental uniparental disomy (UPD): review and lessons from rare chromosomal complements

Kotzot¹

2001

Journal of Medical Genetics

123

107

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“…Possibly because of this assumption, the origin of the rearrangement has only been investigated in seven reports and in none do the two cell lines carry different aberrant chromosomes. [19][20][21][22][23][24][25] In three reports a meiotic error occurred first, followed by either a loss or a rearrangement of the trisomic chromosome. 19 22 24 The finding in this patient reinforces the idea that many chromosomal rearrangements occurring in mosaic people may have their origin during meiosis.…”

Section: Discussionmentioning

confidence: 99%

Mosaicism del(8p)/inv dup(8p) in a dysmorphic female infant: a mosaic formed by a meiotic error at the 8p OR gene and an independent terminal deletion event

Vermeesch¹,

Thoelen²,

Salden³

et al. 2003

Journal of Medical Genetics

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“…More than 30 cases of partial trisomy 16p have now been described and the pattern of malformations and anomalies in the patients is strikingly similar. [18][19][20][21] This syndrome is associated with developmental delay, recurrent respiratory infections, seizures, congenital heart defects, renal and genitourinary anomalies, and cleft palate. Characteristic facial features include scant hair, micrognathia, hypertelorism, upward slanting palpebral fissures, low set ears, a long philtrum and thin upper lip, overlapping fingers, and an abnormally placed thumb.…”

Section: Discussionmentioning

confidence: 99%

"Molecular rulers" for calibrating phenotypic effects of telomere imbalance

Martin

Waggoner

Wong

et al. 2002

Journal of Medical Genetics

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As a result of the increasing use of genome wide telomere screening, it has become evident that a significant proportion of people with idiopathic mental retardation have subtle abnormalities involving the telomeres of human chromosomes. However, during the course of these studies, there have also been telomeric imbalances identified in normal people that are not associated with any apparent phenotype. We have begun to scrutinise cases from both of these groups by determining the extent of the duplication or deletion associated with the imbalance. Five cases were examined where the telomere rearrangement resulted in trisomy for the 16p telomere. The size of the trisomic segment ranged from ∼4-7 Mb and the phenotype included mental and growth retardation, brain malformations, heart defects, cleft palate, pancreatic insufficiency, genitourinary abnormalities, and dysmorphic features. Three cases with telomeric deletions without apparent phenotypic effects were also examined, one from 10q and two from 17p. All three deletions were inherited from a phenotypically normal parent carrying the same deletion, thus without apparent phenotypic effect. The largest deletion among these cases was ∼600 kb on 17p. Similar studies are necessary for all telomeric regions to differentiate between those telomeric rearrangements that are pathogenic and those that are benign variants. Towards this goal, we are developing "molecular rulers" that incorporate multiple clones at each telomere that span the most distal 5 Mb region. While telomere screening has enabled the identification of telomere rearrangements, the use of molecular rulers will allow better phenotype prediction and prognosis related to these findings. U nbalanced submicroscopic telomere rearrangements are a significant cause of idiopathic mental retardation with or without congenital malformations, accounting for approximately 5% of these cases. [1][2][3][4][5][6][7] With the development of a second generation set of telomere specific clones, 8 telomere screening is now readily available in many laboratories and is being used extensively in the evaluation of children with mental retardation and congenital anomalies. The results of these investigations are not only providing explanations for previously unexplained cases of mental retardation, but are also further defining the frequency of telomeric rearrangements in various clinical populations and clarifying the phenotype associated with these rearrangements. Furthermore, during the course of these studies, telomeric imbalances have also been identified in normal subjects without any apparent phenotype.3 5 6 9 These observations suggest that not all telomere imbalances result in a phenotype and that the lack of phenotypic effect may be related to the size of the rearrangement or the involvement of regions of the genome that are tolerant to dosage imbalances.Despite these advances, there is a paucity of information regarding the genotype/phenotype correlations of many of the telomere imbalances discovered, complicating t...

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Trisomy First, Translocation Second, Uniparental Disomy and Partial Trisomy Third: A New Mechanism for Complex Chromosomal Aneuploidy

Cited by 33 publications

References 8 publications

Complex and segmental uniparental disomy (UPD): review and lessons from rare chromosomal complements

Complex and segmental uniparental disomy (UPD): review and lessons from rare chromosomal complements

Mosaicism del(8p)/inv dup(8p) in a dysmorphic female infant: a mosaic formed by a meiotic error at the 8p OR gene and an independent terminal deletion event

"Molecular rulers" for calibrating phenotypic effects of telomere imbalance

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