Buccal cell FISH and blood PCR-Y detect high rates of X chromosomal mosaicism and Y chromosomal derivatives in patients with Turner syndrome

Freriks, K.; Timmers, Henri J L M; Netea‐Maier, Romana T.; Beerendonk, C.C.M.; Otten, Barto J.; Velden, Janiëlle A E M van Alfen-van der; Traas, Maaike A. F.; Mieloo, Hanneke; Zande, Guillaume W. H. J. F. van de; Hoefsloot, Lies H.; Hermus, A.R.M.M.; Smeets, Dominique

doi:10.1016/j.ejmg.2013.07.008

Cited by 50 publications

(50 citation statements)

References 22 publications

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“…In fact, upon invasive growth, most tumor cells lose the expression of TSPY, but in the pre-invasive stage its presence supports identification of malignant germ cells as compared to germ cells delayed in their maturation [Kaprova-Pleskacova et al, 2014]. Interestingly, Turner syndrome patients may have an increased risk of gonadal GCC, which is likely related to the hidden (mosaic) presence of the GBY region [Bianco et al, 2006;Freriks et al, 2013].…”

Section: Gby Regionmentioning

confidence: 96%

Histological Assessment of Gonads in DSD: Relevance for Clinical Management

Spoor

Oosterhuis²,

Hersmus³

et al. 2017

Sex Dev

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Malignant gonadal germ cell tumors, referred to as germ cell cancers (GCC), occur with increased frequency in individuals who have specific types of differences (disorders) of sex development (DSD). Recent population-based studies have identified new environmental and genetic risk factors that have led to a ‘genvironment' hypothesis, which may potentially be helpful in risk assessment in DSD-related GCC. In DSD, the malignancy risk is highly heterogeneous, but recent studies allow now to discriminate between high- and low-risk conditions. Gonadal biopsy is in some cases the best procedure of choice to assess the risk, and with the availability of immunohistochemical biomarkers [OCT3/4 (POU5F1), TSPY, SOX9, FOXL2 and KITLG (SCF)], a reliable classification of GCC and its precursors can be made. The opportunities in the field of virtual diagnostic pathology will be presented, having possibilities for rare diseases in general and DSD specifically. It is expected that the International DSD Registry will stimulate international collaborations, facilitating better diagnostic procedures as well as research.

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Section: Gby Regionmentioning

confidence: 96%

Histological Assessment of Gonads in DSD: Relevance for Clinical Management

Spoor

Oosterhuis²,

Hersmus³

et al. 2017

Sex Dev

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“…Moreover, these patients can have tissue-specific mosaicism. A study from the Netherlands has shown that 30.2% of girls with 45,X monosomy according to classic karyotype analysis have buccal cell mosaicism according to FISH [Freriks et al, 2013]. In 5 patients, the additional cell lines contained a Y chromosome.…”

Section: Discussionmentioning

confidence: 99%

Molecular Detection and Incidence of Y Chromosomal Material in Patients with Turner Syndrome

Rojek

Obara-Moszynska

Kolesinska

et al. 2017

Sex Dev

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The presence of a Y chromosome in patients with Turner syndrome (TS) is a risk factor for the development of gonadal tumor and/or virilization. With conventional cytogenetic analysis, some cells containing a Y chromosome can be missed. The aim of this study was to determine the presence and incidence of Y chromosome-derived material in TS patients using PCR and the markers SRY, DYZ1, DYZ3, DYS132, ZFY, and TSPY. Fifty-five TS patients (aged 5.5-26.75 years) were analyzed. A total of 17/55 (30.9%) were Y-positive, but only 7/17 had a Y chromosome in their karyotype and underwent gonadectomy. In 2 of these patients (28.6%), histopathologic examination revealed gonadoblastoma and dysgerminoma, respectively. In 8 patients in the studied group (8/55; 14.5%), the TSPY gene was detected, and the SRY gene (or a fragment) was identified in 9(3)/55 patients. No coding region mutations were observed in these SRY-positive patients. In conclusion, we have shown a high prevalence of Y chromosomal material in TS. Y markers were also observed in patients who had no Y chromosome in their karyotype, and PCR is very precise in detecting the presence of genetic material from the Y chromosome. Further follow-up of these Y-positive TS patients is mandatory.

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“…In general, the diagnosis of TS is based on karyotyping of blood lymphocytes; however, as this technique does not exclude tissue mosaicism or low-grade mosaicism in the blood, other tests such as FISH with X and Y specific probes or PCR-Y can be considered, which can be performed on either blood samples or other tissue types [2,3,4]. The main indication for this is the associated risk of GB if mosaicism for a Y chromosome is detected [16,17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Diagnosis is made through G-banded karyotype analysis of blood chromosomes following a clinical suspicion based on the presence of one or more of the above features. Current recommendations are to analyse a minimum of 30 cells to exclude mosaicism of over 10%, in 95% of analyses, and to detect any Y chromosome material [2,3,4]. …”

Section: Introductionmentioning

confidence: 99%

Early Bilateral Gonadoblastoma in a Young Child with Mosaicism for Turner Syndrome and Trisomy 18 with Y Chromosome

MacMahon

O’Sullivan²,

McDermott³

et al. 2016

Horm Res Paediatr

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Mosaic Turner syndrome (TSM) commonly occurs in the form of 45,X/46,XX and 45,X/46,X,i(X)(q10). Mosaicism for a Y chromosome, 45,X/46,XY, has been well documented and is associated with increased risk of gonadoblastoma (GB). To date, there are only six reported cases of TSM with a trisomy 18 karyotype, and only two of these were phenotypically female with 45,X/47,XY,+18 karyotype. We present the case of a phenotypically female infant born with dysmorphic features. G-banded karyotype and interphase FISH of blood showed 45,X in 95% and 47,XY,+18 (trisomy 18) in 5% of cells analysed. However, interphase FISH of buccal cells showed only the presence of the 45,X cell line. Due to the presence of Y chromosome material, elective gonadectomy was performed at 13 months of age. There were bilateral streak ovaries with early evidence of GB bilaterally, a rudimentary uterus and bilateral fallopian tubes with unilateral ectopic adrenal tissue identified histologically. Interphase FISH of the gonadal tissue was similar to the blood findings with 45,X in 86% of cells and 47,XY,+18 in 14% of cells analysed. This case highlights a rare karyotype of TSM and trisomy 18 in the same patient and is the first reporting the associated finding of bilateral GB.

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Buccal cell FISH and blood PCR-Y detect high rates of X chromosomal mosaicism and Y chromosomal derivatives in patients with Turner syndrome

Cited by 50 publications

References 22 publications

Histological Assessment of Gonads in DSD: Relevance for Clinical Management

Histological Assessment of Gonads in DSD: Relevance for Clinical Management

Molecular Detection and Incidence of Y Chromosomal Material in Patients with Turner Syndrome

Early Bilateral Gonadoblastoma in a Young Child with Mosaicism for Turner Syndrome and Trisomy 18 with Y Chromosome

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