scholarly journals Insertion of an SVA Element in MSH2 as a Novel Cause of Lynch Syndrome

2020 ◽  
Author(s):  
Ciyu Yang ◽  
Yirong Li ◽  
Magan Trottier ◽  
Michael Farrell ◽  
Vikas Rai ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
Antisense Orientation ◽  
The Family ◽  
Long Range Pcr ◽  
Early Onset Colorectal Cancer ◽  
Generation Sequencing

Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). Insertions of retrotransposons in MMR genes have been reported as a rare cause of LS. Here, we present a novel SINE-VNTR-Alu (SVA) insertion in exon 12 of MSH2 in an individual with early-onset colorectal cancer and strong LS family history. RT-PCR analysis indicated a larger aberrant MSH2 transcript in one of the family members. MSK-IMPACT next-generation sequencing testing and long-range PCR revealed an insertion in MSH2 exon 12 at the c.1972 position in an antisense orientation. The insertion was further characterized as an SVA element approximately 3 kb in length, belonging to the SVA_F1 family of retrotransposons.

scholarly journals Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Francesca Duraturo ◽  
Angela Cavallo ◽  
Raffaella Liccardo ◽  
Bianca Cudia ◽  
Marina De Rosa ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Germ Line ◽  
Point Mutations ◽  
Low Frequency ◽  
Genomic Rearrangements ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
Large Genomic Rearrangements ◽  
Large Deletions ◽  
Long Range Pcr

Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainlyMLH1andMSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in theMLH1andMSH2genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in theMLH1,MSH2, andMSH6genes. We identified a large novel deletion in theMSH2gene, including exon 6 in one of the patients analysed (1.6% frequency). This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement withinMSH2gene and showed that large deletions or duplications inMLH1andMSH2genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

scholarly journals Novel Mutations inMLH1andMSH2Genes in Mexican Patients with Lynch Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jose Miguel Moreno-Ortiz ◽  
María de la Luz Ayala-Madrigal ◽  
Jorge Román Corona-Rivera ◽  
Manuel Centeno-Flores ◽  
Víctor Maciel-Gutiérrez ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
High Performance ◽  
Autosomal Dominant ◽  
Immunohistochemical Analysis ◽  
Compound Heterozygous ◽  
Nuclear Staining ◽  
Dna Mismatch ◽  
Two Samples ◽  
Early Onset Colorectal Cancer ◽  
Mexican Patients

Background. Lynch Syndrome (LS) is characterized by germline mutations in the DNA mismatch repair (MMR) genesMLH1,MSH2,MSH6,andPMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC) and extracolonic tumors. The aim of this study was to identify mutations inMMRgenes in three Mexican patients with LS.Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC), and Sanger sequencing complemented the analysis.Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found inMLH1gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del) and c.1852_1853delinsGC (p.K618A) in exon 16. In theMSH2gene, we identified mutation c.638dupT (p.L213fs) in exon 3.Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel.

scholarly journals Novel viruses detected in bats in the Republic of Korea

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sook-Young Lee ◽  
Chul-Un Chung ◽  
Jun Soo Park ◽  
Jae-Ku Oem
Keyword(s):  
Genetic Relationships ◽  
Rt Pcr ◽  
Entire Genome ◽  
Rotavirus A ◽  
Zoonotic Viruses ◽  
Feces Sample ◽  
The Family ◽  
The Republic ◽  
Viral Sequences ◽  
Generation Sequencing

AbstractBats are natural reservoirs for potential zoonotic viruses. In this study, next-generation sequencing was performed to obtain entire genome sequences of picornavirus from a picornavirus-positive bat feces sample (16BF77) and to explore novel viruses in a pooled bat sample (16BP) from samples collected in South Korea, 2016. Fourteen mammalian viral sequences were identified from 16BF77 and 29 from 16BP, and verified by RT-PCR. The most abundant virus in 16BF77 was picornavirus. Highly variable picornavirus sequences encoding 3Dpol were classified into genera Kobuvirus, Shanbavirus, and an unassigned group within the family Picornaviridae. Amino acid differences between these partial 3Dpol sequences were ≥ 65.7%. Results showed that one bat was co-infected by picornaviruses of more than two genera. Retrovirus, coronavirus, and rotavirus A sequences also were found in the BP sample. The retrovirus and coronavirus genomes were identified in nine and eight bats, respectively. Korean bat retroviruses and coronavirus demonstrated strong genetic relationships with a Chinese bat retrovirus (RfRV) and coronavirus (HKU5-1), respectively. A co-infection was identified in one bat with a retrovirus and a coronavirus. Our results indicate that Korean bats were multiply infected by several mammal viruses.

A new strategy to screen MMR genes in Lynch Syndrome: HA-CAE, MLPA and RT-PCR

2009 ◽  
Vol 45 (8) ◽  
pp. 1485-1493 ◽  
Author(s):  
Lucia Perez-Cabornero ◽  
Eladio Velasco ◽  
Mar Infante ◽  
David Sanz ◽  
Enrique Lastra ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Rt Pcr ◽  
Mmr Genes ◽  
New Strategy

Prenatal Detection of PIK3CA-related Overgrowth Spectrum in Cultured Amniocytes Using Long-range PCR and Next-generation Sequencing

2017 ◽  
Vol 20 (1) ◽  
pp. 54-57 ◽  
Author(s):  
Elizabeth Quinlan-Jones ◽  
Denise Williams ◽  
Charlotte Bell ◽  
Claire Miller ◽  
Carolyn Gokhale ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Phenotypic Expression ◽  
The Body ◽  
The Family ◽  
The Central Nervous System ◽  
Perinatal Management ◽  
Spectrum Disorders ◽  
Long Range Pcr ◽  
Generation Sequencing ◽  
Ultrasound Features

Mutations in PIK3CA are associated with overgrowth spectrum disorders including excessive growth in some areas of the body and the central nervous system. Alterations in PIK3CA occur as somatic, postzygotic events and confer a mosaic genotype with variability in phenotypic expression being commonly observed. We describe the second reported prenatal diagnosis of a PIK3CA-related overgrowth spectrum disorder. The prenatal ultrasound features in this case enabled the presumptive, prospective diagnosis to be made which was then confirmed by genetic testing. Subsequent parental testing for mutations in PIK3CA demonstrated normal genotypes. Identification of this mutation prenatally enabled prospective information to be provided to the family and facilitated multidisciplinary perinatal management.

scholarly journals Novel Implications in Molecular Diagnosis of Lynch Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Raffaella Liccardo ◽  
Marina De Rosa ◽  
Paola Izzo ◽  
Francesca Duraturo
Keyword(s):  
Lynch Syndrome ◽  
Clinical Manifestations ◽  
Mendelian Inheritance ◽  
Dna Mismatch ◽  
Variants Of Unknown Significance ◽  
Mmr Genes ◽  
Risk Alleles ◽  
Detection Analysis ◽  
Unknown Significance ◽  
Analytical Strategies

About 10% of total colorectal cancers are associated with known Mendelian inheritance, as Familial Adenomatous Polyposis (FAP) and Lynch syndrome (LS). In these cancer types the clinical manifestations of disease are due to mutations in high-risk alleles, with a penetrance at least of 70%. The LS is associated with germline mutations in the DNA mismatch repair (MMR) genes. However, the mutation detection analysis of these genes does not always provide informative results for genetic counseling of LS patients. Very often, the molecular analysis reveals the presence of variants of unknown significance (VUSs) whose interpretation is not easy and requires the combination of different analytical strategies to get a proper assessment of their pathogenicity. In some cases, these VUSs may make a more substantial overall contribution to cancer risk than the well-assessed severe Mendelian variants. Moreover, it could also be possible that the simultaneous presence of these genetic variants in several MMR genes that behave as low risk alleles might contribute in a cooperative manner to increase the risk of hereditary cancer. In this paper, through a review of the recent literature, we have speculated a novel inheritance model in the Lynch syndrome; this could pave the way toward new diagnostic perspectives.

scholarly journals Production of transgenic carnation with antisense ACS (1-aminocyclopropane44-carboxy late synthase) gene

2000 ◽  
Vol 6 (4) ◽  
Author(s):  
E. Kiss ◽  
A. Veres ◽  
Zs. Galli ◽  
N. Nagy ◽  
E. Tóth ◽  
...  
Keyword(s):  
Ethylene Production ◽  
Mrna Level ◽  
Dianthus Caryophyllus ◽  
Pcr Analysis ◽  
Vase Life ◽  
Rt Pcr ◽  
Transgene Integration ◽  
Putative Transformants ◽  
Antisense Orientation ◽  
Npt Ii

Dianthus chinensis and Dianthus caryophyllus varieties were tested for shoot regeneration from leaf and petal explants and transformed with Agrobacterium tuniefaciens strains (EHA 105 and LBA 4404) harbouring an apple derived ACS cDNA in antisense orientation in order to reduce ethylene production and influence the ethylene dependant traits in carnation. After transformation regenerating shoots were selected on MS medium containing 50-75-100-125-150 mg/1 kanamycin and supplemented with 1 mg/1 BA, 0.2 mg/1 NAA. Transgene integration was proved by PCR analysis with npt II spcific primers followed by Southern hybridisation of DNA isolated from green shoots on medium containing 150 mg/1 kanamycin. Several putative transformants were subjected to RT-PCR in order to examine the npt 11 expression at mRNA level. Both the transformant and the non-transformant plants were potted into glasshouse to observe the effect of changed ethylene production on flowering time, petal senescence and vase life.  

scholarly journals Clinical and genetic aspects of differential diagnostics of hereditary non-polyposis colorectal cancer

2019 ◽  
Vol 6 (2) ◽  
pp. 21-27
Author(s):  
A. V. Semyanikhina ◽  
A. O. Rasulov ◽  
L. N. Lyubchenko
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Heterogeneous Group ◽  
Differential Diagnostics ◽  
Genetic Characteristics ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
Long Time

Lynch syndrome was synonymous with hereditary non-polyposis colorectal cancer for a long time, however, mapping of the DNA mismatch repair (MMR) genes has led to distinguish Lynch syndrome as an independent syndromic unit from a number of Lynch-like syndromes that phenotypically mimic with the most frequent hereditary variant of colon cancer but genetically representing quite a heterogeneous group. This article presents up to date clinical and genetic characteristics of Lynch syndrome and Lynch-like conditions.

Quantitative RT-PCR Analysis of MMR Genes on EUS-Guided FNA Samples From Focal Pancreatic Lesions

2011 ◽  
Author(s):  
Dan Ionuţ Gheonea ◽  
Marius Eugen Ciurea ◽  
Adrian Săftoiu ◽  
Mihai Ioana
Keyword(s):  
Pcr Analysis ◽  
Rt Pcr ◽  
Mmr Genes

scholarly journals Oligonucleotide-directed mutagenesis screen to identify pathogenic Lynch syndrome-associated MSH2 DNA mismatch repair gene variants

2016 ◽  
Vol 113 (15) ◽  
pp. 4128-4133 ◽  
Author(s):  
Hellen Houlleberghs ◽  
Marleen Dekker ◽  
Hildo Lantermans ◽  
Roos Kleinendorst ◽  
Hendrikus Jan Dubbink ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Embryonic Stem ◽  
Mismatch Repair Gene ◽  
Missense Mutations ◽  
Repair Gene ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
Pathogenic Variants

Single-stranded DNA oligonucleotides can achieve targeted base-pair substitution with modest efficiency but high precision. We show that “oligo targeting” can be used effectively to study missense mutations in DNA mismatch repair (MMR) genes. Inherited inactivating mutations in DNA MMR genes are causative for the cancer predisposition Lynch syndrome (LS). Although overtly deleterious mutations in MMR genes can clearly be ascribed as the cause of LS, the functional implications of missense mutations are often unclear. We developed a genetic screen to determine the pathogenicity of these variants of uncertain significance (VUS), focusing on mutator S homolog 2 (MSH2). VUS were introduced into the endogenous Msh2 gene of mouse embryonic stem cells by oligo targeting. Subsequent selection for MMR-deficient cells using the guanine analog 6-thioguanine allowed the detection of MMR-abrogating VUS. The screen was able to distinguish weak and strong pathogenic variants from polymorphisms and was used to investigate 59 Msh2 VUS. Nineteen of the 59 VUS were identified as pathogenic. Functional assays revealed that 14 of the 19 detected variants fully abrogated MMR activity and that five of the detected variants attenuated MMR activity. Implementation of the screen in clinical practice allows proper counseling of mutation carriers and treatment of their tumors.

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