genetic mutations
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2022 ◽  
Vol 23 (2) ◽  
pp. 953
Author(s):  
Anna Jaruga ◽  
Jakub Ksiazkiewicz ◽  
Krystian Kuzniarz ◽  
Przemko Tylzanowski

Many complex molecular interactions are involved in the process of craniofacial development. Consequently, the network is sensitive to genetic mutations that may result in congenital malformations of varying severity. The most common birth anomalies within the head and neck are orofacial clefts (OFCs) and prognathism. Orofacial clefts are disorders with a range of phenotypes such as the cleft of the lip with or without cleft palate and isolated form of cleft palate with unilateral and bilateral variations. They may occur as an isolated abnormality (nonsyndromic—NSCLP) or coexist with syndromic disorders. Another cause of malformations, prognathism or skeletal class III malocclusion, is characterized by the disproportionate overgrowth of the mandible with or without the hypoplasia of maxilla. Both syndromes may be caused by the presence of environmental factors, but the majority of them are hereditary. Several mutations are linked to those phenotypes. In this review, we summarize the current knowledge regarding the genetics of those phenotypes and describe genotype–phenotype correlations. We then present the animal models used to study these defects.


2022 ◽  
pp. 088532822110658
Author(s):  
Keying Xue ◽  
Bingqing Luo ◽  
Xiaoqing Li ◽  
Weixian Deng ◽  
Chunyan Zeng ◽  
...  

This study was designed to investigate the feasibility of genetic testing using circulating tumor cells (CTCs) instead of tumor tissues in lung adenocarcinoma to break through its limitation. Separation system for epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), and Vimentin expressing CTCs was constructed and used to capture CTCs in the blood samples of 57 patients with lung adenocarcinoma. Genetic mutations of genes involved in targeted therapies were detected by next-generation sequencing (NGS) in tissues from these patients. Blood CTC samples with the gene mutations identified by tissue-NGS were selected and corresponding gene mutations were detected by Sanger sequencing. The specificity of the CTC separation system was 95.48% and the sensitivity was 90.85%. The average number of CTCs in the blood of patients with lung adenocarcinoma was 12.47/7.5 mL. Comparison of the tissue-NGS with the CTC-Sanger sequencing showed that the consistencies of genetic mutations of EGFR ( n = 24), KRAS ( n = 9), TP53 ( n = 19), BRAF ( n = 1), ERBB2 ( n = 2), and PIK3CA ( n = 3) were 92.31%, 75.00%, 86.36%, 50.00%, 66.67%, and 75.00%, with an overall consistency of 84.06%. The CTC separation system established in this study shows high specificity and sensitivity. CTCs can be used as a suitable alternative to tumor tissues that are difficult to obtain in clinical practice and overcome the difficulties in tumor tissue collection, which is of significance in guiding clinical medication and individualized treatment with significant clinical application value in terms of genetic testing for targeted therapies in tumor treatment.


2022 ◽  
Vol 12 ◽  
Author(s):  
Kevin L. Webb ◽  
Paolo B. Dominelli ◽  
Sarah E. Baker ◽  
Stephen A. Klassen ◽  
Michael J. Joyner ◽  
...  

Humans elicit a robust series of physiological responses to maintain adequate oxygen delivery during hypoxia, including a transient reduction in hemoglobin-oxygen (Hb-O2) affinity. However, high Hb-O2 affinity has been identified as a beneficial adaptation in several species that have been exposed to high altitude for generations. The observed differences in Hb-O2 affinity between humans and species adapted to high altitude pose a central question: is higher or lower Hb-O2 affinity in humans more advantageous when O2 availability is limited? Humans with genetic mutations in hemoglobin structure resulting in high Hb-O2 affinity have shown attenuated cardiorespiratory adjustments during hypoxia both at rest and during exercise, providing unique insight into this central question. Therefore, the purpose of this review is to examine the influence of high Hb-O2 affinity during hypoxia through comparison of cardiovascular and respiratory adjustments elicited by humans with high Hb-O2 affinity compared to those with normal Hb-O2 affinity.


Author(s):  
F. Tiso ◽  
T. N. Koorenhof-Scheele ◽  
E. Huys ◽  
J. H. A. Martens ◽  
A. O. de Graaf ◽  
...  

AbstractAcute myeloid leukemia (AML) is a highly heterogeneous disease showing dynamic clonal evolution patterns over time. Various subclones may be present simultaneously and subclones may show a different expansion pattern and respond differently to applied therapies. It is already clear that immunophenotyping and genetic analyses may yield overlapping, but also complementary information. Detailed information on the genetic make-up of immunophenotypically defined subclones is however scarce. We performed error-corrected sequencing for 27 myeloid leukemia driver genes in 86, FACS-sorted immunophenotypically characterized normal and aberrant subfractions in 10 AML patients. We identified three main scenarios. In the first group of patients, the two techniques were equally well characterizing the malignancy. In the second group, most of the isolated populations did not express aberrant immunophenotypes but still harbored several genetic aberrancies, indicating that the information obtained only by immunophenotyping would be incomplete. Vice versa, one patient was identified in which genetic mutations were found only in a small fraction of the immunophenotypically defined malignant populations, indicating that the genetic analysis gave an incomplete picture of the disease. We conclude that currently, characterization of leukemic cells in AML by molecular and immunophenotypic techniques is complementary, and infer that both techniques should be used in parallel in order to obtain the most complete view on the disease.


2022 ◽  
Vol 117 (1) ◽  
Author(s):  
Gerd Heusch

AbstractHeart failure is a clinical syndrome where cardiac output is not sufficient to sustain adequate perfusion and normal bodily functions, initially during exercise and in more severe forms also at rest. The two most frequent forms are heart failure of ischemic origin and of non-ischemic origin. In heart failure of ischemic origin, reduced coronary blood flow is causal to cardiac contractile dysfunction, and this is true for stunned and hibernating myocardium, coronary microembolization, myocardial infarction and post-infarct remodeling, possibly also for the takotsubo syndrome. The most frequent form of non-ischemic heart failure is dilated cardiomyopathy, caused by genetic mutations, myocarditis, toxic agents or sustained tachyarrhythmias, where alterations in coronary blood flow result from and contribute to cardiac contractile dysfunction. Hypertrophic cardiomyopathy is caused by genetic mutations but can also result from increased pressure and volume overload (hypertension, valve disease). Heart failure with preserved ejection fraction is characterized by pronounced coronary microvascular dysfunction, the causal contribution of which is however not clear. The present review characterizes the alterations of coronary blood flow which are causes or consequences of heart failure in its different manifestations. Apart from any potentially accompanying coronary atherosclerosis, all heart failure entities share common features of impaired coronary blood flow, but to a different extent: enhanced extravascular compression, impaired nitric oxide-mediated, endothelium-dependent vasodilation and enhanced vasoconstriction to mediators of neurohumoral activation. Impaired coronary blood flow contributes to the progression of heart failure and is thus a valid target for established and novel treatment regimens.


2022 ◽  
Vol 23 (1) ◽  
pp. 552
Author(s):  
Jaya Bagaria ◽  
Eva Bagyinszky ◽  
Seong Soo A. An

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that was originally discovered in the population from the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region in Quebec. Although the disease progression of ARSACS may start in early childhood, cases with later onset have also been observed. Spasticity and ataxia could be common phenotypes, and retinal optic nerve hypermyelination is detected in the majority of patients. Other symptoms, such as pes cavus, ataxia and limb deformities, are also frequently observed in affected individuals. More than 200 mutations have been discovered in the SACS gene around the world. Besides French Canadians, SACS genetics have been extensively studied in Tunisia or Japan. Recently, emerging studies discovered SACS mutations in several other countries. SACS mutations could be associated with pathogenicity either in the homozygous or compound heterozygous stages. Sacsin has been confirmed to be involved in chaperon activities, controlling the microtubule balance or cell migration. Additionally, sacsin may also play a crucial role in regulating the mitochondrial functions. Through these mechanisms, it may share common mechanisms with other neurodegenerative diseases. Further studies are needed to define the exact functions of sacsin. This review introduces the genetic mutations discovered in the SACS gene and discusses its pathomechanisms and its possible involvement in other neurodegenerative diseases.


Author(s):  
Jahnavi Yeturu ◽  
Poongothai Elango ◽  
S. P. Raja ◽  
P. Nagendra Kumar

Genetics is the clinical review of congenital mutation, where the principal advantage of analyzing genetic mutation of humans is the exploration, analysis, interpretation and description of the genetic transmitted and inherited effect of several diseases such as cancer, diabetes and heart diseases. Cancer is the most troublesome and disordered affliction as the proportion of cancer sufferers is growing massively. Identification and discrimination of the mutations that impart to the enlargement of tumor from the unbiased mutations is difficult, as majority tumors of cancer are able to exercise genetic mutations. The genetic mutations are systematized and categorized to sort the cancer by way of medical observations and considering clinical studies. At the present time, genetic mutations are being annotated and these interpretations are being accomplished either manually or using the existing primary algorithms. Evaluation and classification of each and every individual genetic mutation was basically predicated on evidence from documented content built on medical literature. Consequently, as a means to build genetic mutations, basically, depending on the clinical evidences persists a challenging task. There exist various algorithms such as one hot encoding technique is used to derive features from genes and their variations, TF-IDF is used to extract features from the clinical text data. In order to increase the accuracy of the classification, machine learning algorithms such as support vector machine, logistic regression, Naive Bayes, etc., are experimented. A stacking model classifier has been developed to increase the accuracy. The proposed stacking model classifier has obtained the log loss 0.8436 and 0.8572 for cross-validation data set and test data set, respectively. By the experimentation, it has been proved that the proposed stacking model classifier outperforms the existing algorithms in terms of log loss. Basically, minimum log loss refers to the efficient model. Here the log loss has been reduced to less than 1 by using the proposed stacking model classifier. The performance of these algorithms can be gauged on the basis of the various measures like multi-class log loss.


2021 ◽  
Vol 27 (4) ◽  
pp. 7-15
Author(s):  
Monika Shumkova ◽  
Kiril Karamfiloff ◽  
Raya Ivanova ◽  
Kristina Stoyanova ◽  
Dobrin Vassilev

Cardiomyopathies are a heterogeneous group of diseases. The main pathogenetic mechanism is myocardial damage due to genetic mutations. Cardiomyopathies are one of the leading causes of heart failure, sudden cardiac death, and life-threatening arrhythmias. Certain factors associated with poor prognosis determined the prognosis in this group of patients. Survival in different types of cardiomyopathies depends on the time of diagnosis and initial treatment. The types of cardiomyopathies discussed in this review are hypertrophic cardiomyopathy, dilative cardiomyopathy, restrictive cardiomyopathy, left ventricle non-compaction, and arrhythmogenic right ventricular cardiomyopathy.


Author(s):  
Minzhong Yu ◽  
Rachida Bouhenni ◽  
Shree K. Kurup ◽  
Wei He

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