Clinical and genetic characteristics of patients with multiple polyposis of the large bowel negative for APC and MYH gene mutations using conventional methods

2014 ◽  
Vol 48 (1) ◽  
pp. 15-20
Author(s):  
M. Lozynska ◽  
A. Pławski ◽  
Y. Lozynskyy
Keyword(s):  
Large Bowel ◽  
Gene Mutations ◽  
Multiple Polyposis ◽  
Genetic Characteristics ◽  
Myh Gene ◽  
Conventional Methods

4-Jahres-Update der Murano-Studie bestätigt den Stellenwert von Venetoclax in der 2. Therapielinie der CLL

2021 ◽  
pp. 77-79
Author(s):  
Maximilian Schmutz ◽  
Sebastian Sommer
Keyword(s):  
Response Rate ◽  
Residual Disease ◽  
Gene Mutations ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Fixed Duration ◽  
Genetic Characteristics ◽  
Genomic Complexity ◽  
End Of Treatment

<b>Purpose:</b> In previous analyses of the MURANO study, fixed-duration venetoclax plus rituximab (VenR) resulted in improved progression-free survival (PFS) compared with bendamustine plus rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics. <b>Patients and methods:</b> Patients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR. PFS, overall survival (OS), peripheral-blood minimal residual disease (MRD) status, genomic complexity (GC), and gene mutations were assessed. <b>Results:</b> Of 389 patients, 194 were assigned to VenR and 195 to BR. Four-year PFS and OS rates were higher with VenR than BR, at 57.3% and 4.6% (hazard ratio [HR], 0.19; 95% CI, 0.14 to 0.25), and 85.3% and 66.8% (HR, 0.41; 95% CI, 0.26 to 0.65), respectively. Undetectable MRD (uMRD) at end of combination therapy (EOCT) was associated with superior PFS compared with low MRD positivity (HR, 0.50) and high MRD positivity (HR, 0.15). Patients in the VenR arm who received ibrutinib as their first therapy after progression (n = 12) had a reported response rate of 100% (10 of 10 evaluable patients); patients subsequently treated with a venetoclax-based regimen (n = 14) had a reported response rate of 55% (six of 11 evaluable patients). With VenR, the uMRD rate at end of treatment (EOT) was lower in patients with GC than in those without GC (<i>P</i> = 0.042); higher GC was associated with shorter PFS. Higher MRD positivity rates were seen with <i>BIRC3</i> and <i>BRAF</i> mutations at EOCT and with <i>TP53, NOTCH1, XPO1,</i> and <i>BRAF</i> mutations at EOT. <b>Conclusion:</b> Efficacy benefits with fixed-duration VenR are sustained and particularly durable in patients who achieve uMRD. Salvage therapy with ibrutinib after VenR achieved high response rates. Genetic mutations and GC affected MRD rates and PFS. <b>Trial registration:</b> ClinicalTrials.gov NCT02005471.

scholarly journals Study of The Collagen Type VI Alpha 3 (COL6A3) Gene in Parkinson’s Disease

2021 ◽  
Author(s):  
Chong-Yao Jin ◽  
Ran Zheng ◽  
Zhi-Hao Lin ◽  
Nai-Jia Xue ◽  
Ying Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Collagen Type ◽  
Gene Mutations ◽  
Compound Heterozygous ◽  
Genetic Characteristics ◽  
Increased Risk ◽  
Collagen Type Vi ◽  
Chinese Cohort ◽  
Aggregate Burden

Abstract Background To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. Methods We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. Results First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified seven novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.03). Conclusion An increased aggregate burden of the COL6A3 gene was detected in patients with PD.

scholarly journals Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk

2004 ◽  
Vol 96 (21) ◽  
pp. 1631-1634 ◽  
Author(s):  
M. E. Croitoru ◽  
S. P. Cleary ◽  
N. Di Nicola ◽  
M. Manno ◽  
T. Selander ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Gene Mutations ◽  
Colorectal Cancer Risk ◽  
Myh Gene

scholarly journals Detection and Analysis of Gene Mutations in Patients with Glanzmann's Thrombasthenia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2373-2373
Author(s):  
Boyang Sun ◽  
Donglei Zhang ◽  
Huiyuan Li ◽  
Xueqing Dou ◽  
Renchi Yang
Keyword(s):  
Clinical Laboratory ◽  
Conflicts Of Interest ◽  
Gene Mutations ◽  
Adenosine Diphosphate ◽  
Severe Bleeding ◽  
Missense Mutations ◽  
Novel Mutations ◽  
Genetic Characteristics ◽  
Pathogenic Variants ◽  
Standards And Guidelines

Background: Glanzmann thrombasthenia (GT) is a rare inherited disorder of bleeding, and it is characterized by the impaired or absent platelet aggregation to multiple physiologic agonists such as collagen, adenosine diphosphate (ADP), arachidonic acid(AA), but normal reaction to ristocetin. There is qualitative or quantitative defect in platelet integrin αIIbβ3(GPIIb/IIIa). Pathogenic variants of either αIIb or β3 unit could cause GT. The database of gene mutations is continuously updated on the Internet (http://www.hgmd.org); it totally lists 236 variants of ITGA2B gene and 170 variants of ITGB3 gene. Aim: To characterize the clinical manifestation and molecular basis of GT patients in China, and update the pathogenic variants database. Method: Clinical features are evaluated in 104 patients with GT. New generation sequencing was performed with a custom designed panel for the bleeding and platelet disease involving 76 genes, while ITGA2B and ITGB3 were enrolled. Result: The initial bleeding occurred before 1 age in most patients. Incidence of consanguinity is 12.5%. Symptoms lessened with age in about 30% patients. Female patients suffered more severe bleeding than male patients. Fifty different mutations were detected, among which 15 were novel. Most patients were compound heterozygotes and most mutations detected were missense mutations. Among 15 novel mutations, there were 7 missense mutations, 2 nonsense mutations, 2 splicing mutations, 4 frameshift mutations. Pathogenicity of all novel mutations were evaluated according to the standards and guidelines of ACMG. All variants detected were pathogenic or likely pathogenic. Furthermore, c.1750C>T [p.R584X] and c.2333A>C [p.Q778P] in ITGA2B were detected in 10 and 16 unrelated families, strongly suggesting a founder effect. Conclusion: Our study reports the largest cohort of GT in China, describing the clinical, laboratory and genetic characteristics of 104 patients. We found 15 novel pathogenic mutations in ITGA2B and ITGB3 causing GT. Theses novel findings expand the GT mutation spectrum. Disclosures No relevant conflicts of interest to declare.

scholarly journals In Vitro Propagation Strategies of Medicinally Important Berry Crop, Lingonberry (Vaccinium vitis-idaea L.)

Agronomy ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 744
Author(s):  
Samir C. Debnath ◽  
Usha Arigundam
Keyword(s):  
In Vitro Propagation ◽  
Genetic Characteristics ◽  
Current Review ◽  
Small Fruit ◽  
Antioxidant Metabolites ◽  
Health Promoting ◽  
Micropropagated Plants ◽  
Conventional Methods ◽  
Seed Propagation

Lingonberry (Vaccinium vitis-idaea L.) is a health-promoting small fruit crop rich in antioxidant metabolites that helps to reduce the incidence of degenerative diseases. Being heterozygous, lingonberries cannot preserve genetic characteristics through seed propagation. Conventional vegetative propagation, although it produces true-to-type plants, is not economically viable. In vitro propagation can multiply plants much faster than conventional methods. A liquid cultures system under a bioreactor micropropagation system is of significant importance to increase the multiplication rates of in vitro-produced shoots. Enhanced vegetative growth and variation in biochemical constituents are observed in micropropagated plants. Clonal fidelity, although it may be a serious problem for commercial micropropagation, can be verified efficiently by molecular markers. The current review provides detailed and updated information on lingonberry micropropagation along with conventional methods and their effects on morphological, molecular and biochemical characteristics in micropropagated plants, filling the gap in literature.

RESPONSE: Re: Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk

2005 ◽  
Vol 97 (4) ◽  
pp. 321-322
Author(s):  
S. P. Cleary ◽  
M. E. Croitoru ◽  
R. Gryfe ◽  
M. Manno ◽  
M. Cotterchio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Gene Mutations ◽  
Colorectal Cancer Risk ◽  
Myh Gene

scholarly journals Validation of Microarray for the Simultaneous Detection of Common α- and β-Thalassemia Gene Mutations

2019 ◽  
Vol 50 (3) ◽  
pp. 306-312
Author(s):  
Sakorn Pornprasert ◽  
Rinradee Anurak ◽  
Chedtapak Ruengdit ◽  
Nattasit Pienthai ◽  
Monthathip Tookjai ◽  
...  
Keyword(s):  
Simultaneous Detection ◽  
Gene Mutations ◽  
Accurate Method ◽  
Asian Countries ◽  
Medical Sciences ◽  
Chiang Mai ◽  
Genetic Characteristics ◽  
Hemoglobin E ◽  
Reference Methods ◽  
Southeast Asian Countries

Abstract Background Methods for detecting the complex genetic characteristics of α- and β-thalassemias are required for preventing and controlling the outbreak of new cases. Methods We evaluated the accuracy and practical utility of microarray for simultaneous detection of α- and β-thalassemias. A total of 102 DNA specimens, which represented 25 different genotypes, were tested in parallel using the microarray and reference methods used in the thalassemia laboratory of the Associated Medical Sciences–Clinical Services Center (AMS-CSC), Chiang Mai, Thailand. Results A total of 100 (98.0%) DNA specimens were completely concordant between the microarray and reference methods, whereas discrepancies between the different methods were observed in only 2 DNA specimens with homozygous hemoglobin E (HbE). Conclusions The microarray appeared to be a fast, easy to perform, and accurate method for simultaneous detection of α- and β-thalassemias in Thailand and Southeast Asian countries. However, this technique needs to be improved and validated in a larger number of specimens with homozygous HbE before further routine laboratory use.

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