scholarly journals Diagnosis of Familial Wolf-Hirschhorn Syndrome due to a Paternal Cryptic Chromosomal Rearrangement by Conventional and Molecular Cytogenetic Techniques

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Carlos A. Venegas-Vega ◽  
Fernando Fernández-Ramírez ◽  
Luis M. Zepeda ◽  
Karem Nieto-Martínez ◽  
Laura Gómez-Laguna ◽  
...  

The use of conventional cytogenetic techniques in combination with fluorescentin situhybridization (FISH) and single-nucleotide polymorphism (SNP) microarrays is necessary for the identification of cryptic rearrangements in the diagnosis of chromosomal syndromes. We report two siblings, a boy of 9 years and 9 months of age and his 7-years- and 5-month-old sister, with the classic Wolf-Hirschhorn syndrome (WHS) phenotype. Using high-resolution GTG- and NOR-banding karyotypes, as well as FISH analysis, we characterized a pure 4p deletion in both sibs and a balanced rearrangement in their father, consisting in an insertion of 4p material within a nucleolar organizing region of chromosome 15. Copy number variant (CNV) analysis using SNP arrays showed that both siblings have a similar size of 4p deletion (~6.5 Mb). Our results strongly support the need for conventional cytogenetic and FISH analysis, as well as high-density microarray mapping for the optimal characterization of the genetic imbalance in patients with WHS; parents must always be studied for recognizing cryptic balanced chromosomal rearrangements for an adequate genetic counseling.

2005 ◽  
Vol 125 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Emmanuel Jacquot ◽  
Michel Tribodet ◽  
Flora Croizat ◽  
Valérie Balme-Sinibaldi ◽  
Camille Kerlan

2015 ◽  
Vol 172 (5) ◽  
pp. 571-582 ◽  
Author(s):  
Chiara Colato ◽  
Caterina Vicentini ◽  
Silvia Cantara ◽  
Serena Pedron ◽  
Paolo Brazzarola ◽  
...  

ObjectiveChromosomal rearrangements of theRETproto-oncogene is one of the most common molecular events in papillary thyroid carcinoma (PTC). However, their pathogenic role and clinical significance are still debated. This study aimed to investigate the prevalence of RET/PTC rearrangement in a cohort ofBRAFWT PTCs by fluorescencein situhybridization (FISH) and to search a reliable cut-off level in order to distinguish clonal or non-clonal RET changes.DesignFortyBRAFWT PTCs were analyzed by FISH for RET rearrangements. As controls, sixBRAFV600E mutated PTCs, 13 follicular adenomas (FA), and ten normal thyroid parenchyma were also analyzed.MethodsWe performed FISH analysis on formalin-fixed, paraffin-embedded tissue using a commercially available RET break–apart probe. A cut-off level equivalent to 10.2% of aberrant cells was accepted as significant. To validate FISH results, we analyzed the study cohort by qRT-PCR.ResultsSplit RET signals above the cut-off level were observed in 25% (10/40) of PTCs, harboring a percentage of positive cells ranging from 12 to 50%, and in one spontaneous FA (1/13, 7.7%). Overall, the data obtained by FISH matched well with qRT-PCR results. Challenging findings were observed in five cases showing a frequency of rearrangement very close to the cut-off.ConclusionsFISH approach represents a powerful tool to estimate the ratio between broken and non-broken RET tumor cells. Establishing a precise FISH cut-off may be useful in the interpretation of the presence of RET rearrangement, primarily when this strategy is used for cytological evaluation or for targeted therapy.


2018 ◽  
Vol 84 (23) ◽  
Author(s):  
Carlos A. Loncoman ◽  
Carol A. Hartley ◽  
Mauricio J. C. Coppo ◽  
Glenn F. Browning ◽  
Gabriela Beltrán ◽  
...  

ABSTRACT Infectious laryngotracheitis (ILTV; Gallid alphaherpesvirus 1) causes mild to severe respiratory disease in poultry worldwide. Recombination in this virus under natural (field) conditions was first described in 2012 and more recently has been studied under laboratory conditions. Previous studies have revealed that natural recombination is widespread in ILTV and have also demonstrated that recombination between two attenuated ILTV vaccine strains generated highly virulent viruses that produced widespread disease within poultry flocks in Australia. In the United States, natural ILTV recombination has also been detected, but not as frequently as in Australia. To better understand recombination in ILTV strains originating from the United States, we developed a TaqMan single nucleotide polymorphism (SNP) genotyping assay to detect recombination between two virulent U.S. field strains of ILTV (63140 and 1874c5) under experimental in vivo conditions. We also tested the capacity of the Innovax-ILT vaccine (a recombinant vaccine using herpesvirus of turkeys as a vector) and the Trachivax vaccine (a conventionally attenuated chicken embryo origin vaccine) to reduce recombination. The Trachivax vaccine prevented ILTV replication, and therefore recombination, in the trachea after challenge. The Innovax-ILT vaccine allowed the challenge viruses to replicate and to recombine, but at a significantly lower rate than in an unvaccinated group of birds. Our results demonstrate that the TaqMan SNP genotyping assay is a useful tool to study recombination between these ILTV strains and also show that vaccination can limit the number and diversity of recombinant progeny viruses. IMPORTANCE Recombination allows alphaherpesviruses to evolve over time and become more virulent. Historically, characterization of viral vaccines in poultry have mainly focused on limiting clinical disease, rather than limiting virus replication, but such approaches can allow field viruses to persist and evolve in vaccinated populations. In this study, we vaccinated chickens with Gallid alphaherpesvirus 1 vaccines that are commercially available in the United States and then performed coinoculations with two field strains of virus to measure the ability of the vaccines to prevent field strains from replicating and recombining. We found that vaccination reduced viral replication, recombination, and diversity compared to those in unvaccinated chickens, although the extent to which this occurred differed between vaccines. We suggest that characterization of vaccines could include studies to examine the ability of vaccines to reduce viral recombination in order to limit the rise of new virulent field strains due to recombination, especially for those vaccines that are known not to prevent viral replication following challenge.


2020 ◽  
Vol 160 (10) ◽  
pp. 610-624
Author(s):  
Shayer M.I. Alam ◽  
Stephen D. Sarre ◽  
Arthur Georges ◽  
Tariq Ezaz

Agamid lizards (Squamata: Agamidae) are karyotypically heterogeneous. Among the 101 species currently described from Australia, all are from the subfamily Amphibolurinae. This group is, with some exceptions, karyotypically conserved, and all species involving heterogametic sex show female heterogamety. Here, we describe the chromosomes of 2 additional Australian agamid lizards, <i>Tympanocryptis lineata</i> and <i>Rankinia diemensis</i>. These species are phylogenetically and cytogenetically sisters to the well-characterised <i>Pogona vitticeps,</i> but their sex chromosomes and other chromosomal characteristics are unknown. In this study, we applied advanced molecular cytogenetic techniques, such as fluorescence in situ hybridisation (FISH) and cross-species gene mapping, to characterise chromosomes and to identify sex chromosomes in these species. Our data suggest that both species have a conserved karyotype with <i>P. vitticeps</i> but with subtle rearrangements in the chromosomal landscapes. We could identify that <i>T. lineata</i> possesses a female heterogametic system (ZZ/ZW) with a pair of sex microchromosomes, while <i>R. diemensis</i> may have heterogametic sex chromosomes, but this requires further investigations. Our study shows the pattern of chromosomal rearrangements between closely related species, explaining the speciation within Australian agamid lizards of similar karyotypes.


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