Dynamic mosaicism manifesting as loss, gain and rearrangement of an isodicentric Y chromosome in a male child with growth retardation and abnormal external genitalia

Iourov, Ivan Y.; Sg, Vorsanova; Liehr, Thomas; Monakhov, V.V.; Soloviev, Ilia V.; Yurov, Yuri B.

doi:10.1159/000138903

Cited by 25 publications

(31 citation statements)

References 29 publications

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“…After the introduction of molecular cytogenetics [4-7], it became even possible to analyze numerical chromosomal aberrations in non-dividing cells [8]. By that also low-level chromosomal aberrations could be detected in tumor [9-13], various clinical [14-18] and neuronal diseases [19-27], embryonic tissues [28-32] and different tissue types [9, 13, 15, 33-35]. Overall it can be stated that chromosome instability is one of the main causes of large-scale genome variation [36-39].…”

Section: Small Supernumerary Marker Chromosomes (Ssmc)mentioning

confidence: 99%

Somatic Mosaicism in Cases with Small Supernumerary Marker Chromosomes

Liehr

Карамышева²,

Merkaš³

et al. 2010

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Somatic mosaicism is something that is observed in everyday lives of cytogeneticists. Chromosome instability is one of the leading causes of large-scale genome variation analyzable since the correct human chromosome number was established in 1956. Somatic mosaicism is also a well-known fact to be present in cases with small supernumerary marker chromosomes (sSMC), i.e. karyotypes of 47,+mar/46. In this study, the data available in the literature were collected concerning the frequency mosaicism in different subgroups of patients with sSMC. Of 3124 cases with sSMC 1626 (52%) present with somatic mosaicism. Some groups like patients with Emanuel-, cat-eye- or i(18p)- syndrome only tend rarely to develop mosaicism, while in Pallister-Killian syndrome every patient is mosaic. In general, acrocentric and non-acrocentric derived sSMCs are differently susceptible to mosaicism; non-acrocentric derived ones are hereby the less stable ones. Even though, in the overwhelming majority of the cases, somatic mosaicism does not have any detectable clinical effects, there are rare cases with altered clinical outcomes due to mosaicism. This is extremely important for prenatal genetic counseling. Overall, as mosaicism is something to be considered in at least every second sSMC case, array-CGH studies cannot be offered as a screening test to reliably detect this kind of chromosomal aberration, as low level mosaic cases and cryptic mosaics are missed by that.

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Section: Small Supernumerary Marker Chromosomes (Ssmc)mentioning

confidence: 99%

Somatic Mosaicism in Cases with Small Supernumerary Marker Chromosomes

Liehr

Карамышева²,

Merkaš³

et al. 2010

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“…Because Y isochromosomes in human are frequently dicentric [Iourov et al, 2008], we investigated whether or not the horse Y isochromosome has one or 2 closely located centromeres. FISH with a specially designed probe ECAcons70, containing consensus sequences of equine centromeres [Alkan et al, 2011], clearly showed that the horse i(Yq) was monocentric ( fig.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, pure Y chromosome disomy is diagnosed in 1 of 840 human males with only minor phenotypic effects [Gonzalez-Merino et al, 2007]. At the same time, the majority of humans with Y iso chromosomes are cytogenetically mosaics exhibiting various phenotypes of abnormal sexual development [Daniel et al, 1980;Haaf and Schmid, 1990;Codina-Pascual et al, 2004;Iourov et al, 2008].…”

Section: Genetic and Phenotypic Consequences Of Y Isochromosomementioning

confidence: 99%

“…They involve both autosomes and the sex chromosomes [Shaffer and Lupski, 2000;Lupski and Stankiewicz, 2005] with the i(HSAXq) being the most frequently observed (1 in 13,000) isochromosome. Isochromosomes of HSAY are also not uncommon but show considerable variation in rearrangement breakpoints and the number of centromeres [Armendares et al, 1972;Cohen et al, 1973;Giraud et al, 1977;Daniel et al, 1980;Haaf and Schmid, 1990;Hsu, 1994;Yoshida et al, 1997;Codina-Pascual et al, 2004;Iourov et al, 2008]. Because isochromosome formation changes gene dosage, the chromosomes can be associated with tumor formation [Jin et al, 2000], spontaneous abortions [Berend et al, 2000], and developmental and reproductive disorders [Wolff et al, 1996;Codina-Pascual et al, 2004].…”

mentioning

confidence: 99%

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Cytogenetic and Molecular Characterization of Y Isochromosome in a 63XO/64Xi(Yq) Mosaic Karyotype of an Intersex Horse

Das

Lyle

Beehan

et al. 2011

Sex Dev

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Sex chromosome aberrations commonly lead to abnormal sexual development. Here we cytogenetically and molecularly characterized Y isochromosome in an intersex horse. Blood lymphocyte analysis showed a mosaic karyotype with 96% 63,XO and 4% 64,Xi(Y) cells. Molecular analysis of the isochromosome was carried out by fluorescence in situ hybridization and polymerase chain reaction with male-specific and pseudoautosomal markers from the horse Y chromosome. We found that the isochromosome was monocentric, composed of 2 long arms, carrying 2 sets of genes of the pseudoautosomal region (PAR) and the male-specific region of the Y (MSY), including the SRY - thus being genetically equivalent to Y disomy. Sequence analysis of a 1,955-bp region including the SRY exon, the promoter and the UTRs, revealed no mutations in the aberrant Y. The presence of an intact SRY in a small proportion of cells is the proposed cause for the intersex phenotype. Given that the i(Yq) was present in a mosaic form, both post-zygotic and meiotic mechanisms of its origin were proposed. We speculated that nonmosaic 64,Xi(Yq) karyotypes might be rare or absent because of the likely instability of the i(Yq) during cell division. Genetic and phenotypic implications of Y isochromosome formation in other mammals are discussed in the light of the diversity of Y chromosome organization between species.

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“…Because of its meiotic or post-zygotic origin and its mitotic instability, most (90%) idic(Y) chromosomes are present in mosaicism with a 45,X cell line. Depending on the breakpoints and the types of mosaicism, patients with idic(Y) have a wide range of phenotypic manifestations [Tuck-Muller et al, 1995;Iourov et al, 2008]. As previously reviewed, 40.9% of affected individuals were phenotypic females, 31.8% were phenotypic males and 27.3% had different degrees of intersexuality [Hsu, 1994].…”

Section: Discussionmentioning

confidence: 99%

Molecular and Clinical Characteristics of 26 Cases with Structural Y Chromosome Aberrations

Kim

Park

Ryu

et al. 2012

Cytogenet Genome Res

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Structural abnormalities include various types of translocations, inversions, deletions, duplications and isochromosomes. Structural abnormalities of the Y chromosome are estimated to affect less than 1% of the newborn male population and are particularly hazardous for male reproductive function. The objective of this study was to characterize a group of patients with structural abnormalities of the Y chromosome. All patients who visited our laboratory between 2007 and 2010 underwent cytogenetic investigations. Among these, we detected 26 patients with structural abnormalities of the Y chromosome. To confirm the structural Y chromosome alterations, we used special bandings, FISH and multiplex PCR to detect Y chromosome microdeletions. Of the 26 patients presented here, 11 had an isodicentric Y chromosome, 7 had an inversion, 3 had a translocation, 2 had a derivative, 2 had a Yqs and 1 had a deletion. Sixteen were diagnosed with azoospermia, 8 as normal fertile males and 1 as a man who was unable to donate semen due to mental retardation. One of the patients having 45,X/46,X,idic(Y) was reported to be phenotypically female with primary amenorrhea and without uterus. Deletions of the AZFbc region were correlated with the sperm concentration (p < 0.05), but no correlation with the levels of FSH, LH, testosterone, prolactin and estradiol were found. The present report shows that the precise identification of structural Y chromosome aberrations may be clinically important for genetic counseling and assisted reproductive technology treatment.

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Dynamic mosaicism manifesting as loss, gain and rearrangement of an isodicentric Y chromosome in a male child with growth retardation and abnormal external genitalia

Cited by 25 publications

References 29 publications

Somatic Mosaicism in Cases with Small Supernumerary Marker Chromosomes

Somatic Mosaicism in Cases with Small Supernumerary Marker Chromosomes

Cytogenetic and Molecular Characterization of Y Isochromosome in a 63XO/64Xi(Yq) Mosaic Karyotype of an Intersex Horse

Molecular and Clinical Characteristics of 26 Cases with Structural Y Chromosome Aberrations

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