How common is germinal mosaicism that leads to premeiotic aneuploidy in the female?

Abstract Purpose Molecular cytogenetic analysis has confirmed that a proportion of apparently meiotic aneuploidy may be present in the germ cells prior to the onset of meiosis, but there is no clear perception of its frequency. The aim of this review is to assess the evidence for premeiotic aneuploidy from a variety of sources to arrive at an estimate of its overall contribution to oocyte aneuploidy in humans. Methods Relevant scientific literature was covered from 1985 to 2018 by searching PubMed databases with search terms: gonadal/germinal mosaicism, ovarian mosaicism, premeiotic aneuploidy, meiosis and trisomy 21. Additionally, a key reference from 1966 was included. Results Data from over 9000 cases of Down syndrome showed a bimodal maternal age distribution curve, indicating two overlapping distributions. One of these matched the pattern for the control population, with a peak at about 28 years and included all cases that had occurred independently of maternal age, including those due to germinal mosaicism, about 40% of the cohort. The first cytological proof of germinal mosaicism was obtained by fluorescence in situ hybridisation analysis. Comparative genomic hybridisation analysis of oocyte chromosomes suggests an incidence of up to 15% in premeiotic oocytes. Direct investigation of fetal ovarian cells led to variable results for chromosome 21 mosaicism. Conclusions Oocytes with premeiotic errors will significantly contribute to the high level of preimplantation and prenatal death. Data so far available suggests that, depending upon the maternal age, up to 40% of aneuploidy that is present in oocytes at the end of meiosis I may be due to germinal mosaicism.

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Comparison of genomic abnormality in malignant mesothelioma by the site of origin

Journal of Clinical Pathology ◽

10.1136/jclinpath-2014-202465 ◽

2014 ◽

Vol 67 (12) ◽

pp. 1038-1043 ◽

Cited By ~ 11

Author(s):

Maiko Takeda ◽

Takahiko Kasai ◽

Yasunori Enomoto ◽

Masato Takano ◽

Kohei Morita ◽

...

Keyword(s):

Malignant Mesothelioma ◽

In Situ Hybridisation ◽

Homozygous Deletion ◽

Comparative Genomic Hybridisation ◽

Comparative Genomic ◽

Fish Analysis ◽

Fluorescence In Situ Hybridisation ◽

Hybridisation Analysis ◽

Genetic Events

AimsMalignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes are losses in 9p21, 1p36, 22q12 and 14q32, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. We have examined various genomic losses and gains in MM and benign mesothelial proliferation by fluorescence in situ hybridisation (FISH) analysis. 9p21 deletion was reported to be less frequent in peritoneal than in pleural MMs. This study analysed various genomic losses and gains in MM by the site of origin using FISH analysis.Materials and methodsWe performed FISH analysis using paraffin-embedded tissues from 54 cases (40 pleural and 14 peritoneal) of MMs and compared the frequency of genomic abnormality by the site of origin.Results9p21 deletion was shown in 34 of 40 cases (85%) of pleural MMs, and was less frequent in five of 14 cases (36%) of peritoneal MMs (p<0.001) by FISH analysis. By contrast, 5p15 and 7p12 amplification was more significantly frequent in peritoneal than in pleural MMs. No difference between the two sites of MM in other genes was found.Conclusions9p21 homozygous deletion assessed by FISH has been reported to be useful for differentiating MM from reactive mesothelial proliferation, but it should be noted that 9p21 deletion was less frequent in peritoneal MM. Our study suggests that the pathway of the genetic abnormality might vary between pleural and peritoneal MM.

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Clinical and genomic features of adult and paediatric acute leukaemias with ophthalmic manifestations

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2019-000362 ◽

2019 ◽

Vol 4 (1) ◽

pp. e000362

Author(s):

Lisa Stenman Skarsgård ◽

Mattias K. Andersson ◽

Marta Persson ◽

Ann-Cathrine Larsen ◽

Sarah E. Coupland ◽

...

Keyword(s):

Correct Diagnosis ◽

In Situ Hybridisation ◽

University Hospital ◽

Comparative Genomic Hybridisation ◽

Comparative Genomic ◽

Fluorescence In Situ Hybridisation ◽

Genomic Features ◽

Ocular Manifestations ◽

Ophthalmic Manifestations ◽

Genomic Imbalances

ObjectiveTo describe the clinicopathological and genomic features of nine patients with primary and secondary orbital/ocular manifestations of leukaemia.MethodsAll orbital/ocular leukaemic specimens from 1980 to 2009 were collected from the Danish Register of Pathology. In six cases, medical records and formalin-fixed, paraffin-embedded blocks were available. Three cases from the Department of Pathology, Royal Liverpool University Hospital, were also included. Immunophenotypes and MYB oncoprotein expression were ascertained by immunohistochemistry. Genomic imbalances were analysed with comparative genomic hybridisation arrays and oncogene rearrangements with fluorescence in situ hybridisation.ResultsFour patients had B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) and five had acute myeloid leukaemia (AML). Two patients with BCP-ALL and one with AML had primary orbital manifestations of leukaemia. Common symptoms were proptosis, displacement of the eye, and reduced eye mobility in patients with orbital leukaemias and pain, and reduced visual acuity in patients with ocular leukaemias. All patients with primary orbital lesions were alive up to 18 years after diagnosis. All but one patient with secondary ophthalmic manifestations died of relapse/disseminated disease. ETV6 and RUNX1 were rearranged in BCP-ALL, and RUNX1 and KMT2A in AML. Genomic profiling revealed quiet genomes (0–7 aberrations/case). The MYB oncoprotein was overexpressed in the majority of cases.ConclusionsLeukaemias with and without ophthalmic manifestations have similar immunophenotypes, translocations/gene fusions and copy number alterations. Awareness of the clinical spectrum of leukaemic lesions of the eye or ocular region is important to quickly establish the correct diagnosis and commence prompt treatment.

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Imbalances of chromosome 17 in medulloblastomas determined by comparative genomic hybridisation and fluorescence in situ hybridisation

Molecular Pathology ◽

10.1136/mp.53.6.313 ◽

2000 ◽

Vol 53 (6) ◽

pp. 313-319 ◽

Cited By ~ 33

Author(s):

J Nicholson

Keyword(s):

In Situ Hybridisation ◽

Chromosome 17 ◽

Comparative Genomic Hybridisation ◽

Comparative Genomic ◽

Fluorescence In Situ Hybridisation

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ESHRE PGT Consortium good practice recommendations for the detection of structural and numerical chromosomal aberrations†

Human Reproduction Open ◽

10.1093/hropen/hoaa017 ◽

2020 ◽

Vol 2020 (3) ◽

Author(s):

Edith Coonen ◽

Carmen Rubio ◽

Dimitra Christopikou ◽

Eftychia Dimitriadou ◽

Julia Gontar ◽

...

Keyword(s):

Risk Assessment ◽

Best Practice ◽

Good Practice ◽

In Situ Hybridisation ◽

Snp Array ◽

Comparative Genomic Hybridisation ◽

Comparative Genomic ◽

Fluorescence In Situ Hybridisation ◽

Technical Aspects ◽

Practice Recommendations

Abstract The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for PGD, published in 2005 and 2011, are considered outdated, and the development of new papers outlining recommendations for good practice in PGT was necessary. The current paper provides recommendations on the technical aspects of PGT for chromosomal structural rearrangements (PGT-SR) and PGT for aneuploidies (PGT-A) and covers recommendations on array-based comparative genomic hybridisation (aCGH) and next-generation sequencing (NGS) for PGT-SR and PGT-A and on fluorescence in situ hybridisation (FISH) and single nucleotide polymorphism (SNP) array for PGT-SR, including laboratory issues, work practice controls, pre-examination validation, preclinical work-up, risk assessment and limitations. Furthermore, some general recommendations on PGT-SR/PGT-A are formulated around training and general risk assessment, and the examination and post-examination process. This paper is one of a series of four papers on good practice recommendations on PGT. The other papers cover the organisation of a PGT centre, embryo biopsy and tubing and the technical aspects of PGT for monogenic/single-gene defects (PGT-M). Together, these papers should assist everyone interested in PGT in developing the best laboratory and clinical practice possible.

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Chromosome 22q11.21 microduplication in association with hypoplastic left heart syndrome with hypoplastic pulmonary arteries

Cardiology in the Young ◽

10.1017/s104795111300231x ◽

2014 ◽

Vol 25 (1) ◽

pp. 167-170 ◽

Cited By ~ 1

Author(s):

Colin J. McMahon ◽

Conall T. Morgan ◽

Marie T. Greally

Keyword(s):

Hypoplastic Left Heart Syndrome ◽

Fontan Procedure ◽

In Situ Hybridisation ◽

Pulmonary Arteries ◽

Comparative Genomic Hybridisation ◽

Comparative Genomic ◽

Fluorescence In Situ Hybridisation ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Left Heart Syndrome

AbstractWe describe a case of a baby girl born with hypoplastic left heart syndrome consisting of mitral atresia, aortic atresia, hypoplastic ascending aorta, and left ventricle. The pulmonary arteries were hypoplastic, measuring 3 mm. Fluorescence in situ hybridisation analysis demonstrated a microduplication of chromosome 22q11.2. Subsequent array comparative genomic hybridisation showed a gain of 2.3 Mb in one copy of chromosome 22q at band 22q11.21. The proband underwent a successful Norwood procedure with Sano shunt and subsequently underwent bi-directional Glenn shunt and Fontan procedure. This report highlights the association between hypoplastic left heart syndrome with hypoplastic pulmonary arteries and chromosome 22q11.21 microduplication.

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