scholarly journals Danon disease: a case report and literature review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiamin Xu ◽  
Zhu Li ◽  
Yihai Liu ◽  
Xinlin Zhang ◽  
Fengnan Niu ◽  
...  
Keyword(s):  
Frameshift Mutation ◽  
Muscle Fibers ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Danon Disease ◽  
Autophagic Vacuoles ◽  
Femoral Muscle ◽  
Cardiac Muscle Fibers ◽  
Clinical Triad ◽  
Next Generation Sequencing Ngs

Abstract Background Danon disease (DD) is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and mental retardation. It is caused by a defect in the lysosomal-associated membrane protein-2 (LAMP2) gene, which leads to the formation of autophagic vacuoles containing glycogen granule deposits in skeletal and cardiac muscle fibers. So far, more than 50 different mutations in LAMP2 have been identified. Case presentation Here, we report an 18-year-old male patient who was hospitalized for heart failure. Biopsy of the left lateral femoral muscle revealed scattered autophagic vacuoles in the muscle fibers with increased glycogen. Next generation sequencing (NGS) was used to detect gene mutations of the proband sample and a novel frameshift mutation (c.1052delG) has been identified in exon 8 of LAMP2, which leads to truncation of the protein. Conclusion We found a novel frameshift mutation, a hemizygous mutation (c.1052delG) in exon 8 of LAMP2, identified as presenting the hypertrophic cardiomyopathy (HCM) phenotype. Genetic analysis is the gold standard for the diagnosis of DD and is essential to determine appropriate treatment strategies and to confirm the genetic risk of family members.

Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer

2021 ◽  
Author(s):  
Lingyun Zhang ◽  
Zhixiang Ren ◽  
Zhengzheng Su ◽  
Yang Liu ◽  
Tian Yang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Copy Number ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Anaplastic Thyroid Cancer ◽  
Chinese Patients ◽  
Driver Gene ◽  
Phosphatidylinositol 3 Kinase ◽  
Entire Cohort ◽  
Whole Exome

Abstract Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. Results The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. Conclusions This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

scholarly journals Jervell and Lange-Nielsen Syndrome due to a Novel Compound Heterozygous KCNQ1 Mutation in a Chinese Family

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yue Qiu ◽  
Sen Chen ◽  
Xia Wu ◽  
Wen-Juan Zhang ◽  
Wen Xie ◽  
...  
Keyword(s):  
Deaf Child ◽  
Gene Mutations ◽  
Deaf Children ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Qtc Interval ◽  
Cardiac Events ◽  
Life Threatening ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Jervell and Lange-Nielsen syndrome (JLNS) is a rare but severe autosomal recessive disease characterized by profound congenital deafness and a prolonged QTc interval (greater than 500 milliseconds) in the ECG waveforms. The prevalence of JLNS is about 1/1000000 to 1/200000 around the world. However, exceed 25% of JLNS patients suffered sudden cardiac death with kinds of triggers containing anesthesia. Approximately 90% of JLNS cases are caused by KCNQ1 gene mutations. Here, using next-generation sequencing (NGS), we identified a compound heterozygosity for two mutations c.1741A>T (novel) and c.477+5G>A (known) in KCNQ1 gene as the possible pathogenic cause of JLNS, which suggested a high risk of cardiac events in a deaf child. The hearing of this patient improved significantly with the help of cochlear implantation (CI). But life-threatening arrhythmias occurred with a trigger of anesthesia after the end of the CI surgery. Our findings extend the KCNQ1 gene mutation spectrum and contribute to the management of deaf children diagnosed with JLNS for otolaryngologists (especially cochlear implant teams).

scholarly journals Heart structure, serum cholesterol, and adiposity of rats treated with a hypercaloric diet: effectiveness of Citrus sinensis (L.) Osbeck and swimming

2020 ◽  
Vol 21 ◽  
Author(s):  
Beatriz Almeida Rodrigues ◽  
Gabrielle Queiroz Vacari ◽  
Fabiana Cirino dos Santos ◽  
Felipe Perissini ◽  
Matheus Nobile ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Herbal Medicine ◽  
Citrus Sinensis ◽  
Wistar Rats ◽  
Muscle Fibers ◽  
Abdominal Fat ◽  
Tukey Test ◽  
Cardiac Muscle Fibers ◽  
The Right ◽  
Hypercaloric Diet

Abstract This study evaluated the effects of the herbal medicine red orange (Citrus sinensis (L.) Osbeck) and swimming for 84 days on the animal, heart, and abdominal fat weight and the histomorphometric aspects of heart and total cholesterol of Wistar rats. The rats were divided into seven experimental groups of 12 animals each, consisting of a normocaloric diet (Dn), hypercaloric diet (Dh), normocaloric diet and herbal medicine (DnH), hypercaloric diet and herbal medicine (DhH), normocaloric diet and swimming (DnS), hypercaloric diet and swimming (DhS), and hypercaloric diet, swimming, and herbal medicine (DhSH). The data were analyzed statistically by the Tukey test and considered significant when p<0.05. Groups treated with the normocaloric diet had lower abdominal fat weight. The normocaloric diet and herbal medicine (DnH) provided the smallest thickness of the right ventricle. The hypercaloric diet (Dh) reduced the number of cardiomyocytes and the perimeter of cardiac muscle fibers. Swimming and the red orange extract acted synergistically by reducing the deleterious effects of the hypercaloric diet and increasing the thickness of the cardiac chambers and the number of cardiomyocytes. Only the supplementation with the red orange extract did not reduce abdominal fat in rats treated with a hypercaloric diet. Therefore, red orange alone did not promote beneficial changes in the studied data, but its association with swimming increased the number of cardiomyocytes and thickness of muscle fibers, which could contribute to preventing cardiovascular diseases and maintaining health, as well as the regular swimming and a normocaloric diet, which provided less adiposity.

scholarly journals Frequent Mutations in Natural Killer/T Cell Lymphoma

2018 ◽  
Vol 49 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Yanjie Zhang ◽  
Chaoping Li ◽  
Weili Xue ◽  
Mingzhi Zhang ◽  
Zhaoming Li
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Gene Mutations ◽  
T Cell Lymphoma ◽  
Somatic Gene ◽  
Frequent Mutations ◽  
New Biomarkers ◽  
Next Generation Sequencing Ngs

Extranodal natural killer (NK)/T cell lymphoma (ENKTL-NT or NKTCL), with its aggressive nature and poor prognosis, has been widely studied to discover more effective treatment options. Various somatic gene alterations have been identified by traditional Sanger sequencing. However, recently, novel gene mutations in NKTCL have been revealed by next-generation sequencing (NGS) technology, suggesting the potential for novel targeted therapies. This review discusses recurrent aberrations in NKTCL detected by NGS, which can be categorized into three main groups, specifically, tumor suppressors (TP53, DDX3X, and MGA), the JAK/STAT cascade, and epigenetic modifiers (KMT2D, BCOR, ARID1A, and EP300). Some epigenetic dysregulation and DDX3X mutation, which have been rarely identified by traditional sequencing technology, were recently uncovered with high frequencies by NGS. In this review, we summarize the mutational frequencies of various genes in NKTCL. In general, based on our analysis, BCOR is the most frequently mutated gene (16.9%), followed by TP53 (14.7%), and DDX3X (13.6%). The characterization of such genes provides new insight into the pathogenesis of this disease and indicates new biomarkers or therapeutic targets.

Bcl-2, Bcl-x, and Bax Expression by Immunohistochemistry in Inclusion Body Myositis

2001 ◽  
Vol 125 (10) ◽  
pp. 1326-1330
Author(s):  
Richard A. Prayson ◽  
Albert C. Yu
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Staining Pattern ◽  
Apoptotic Cell ◽  
Muscle Fibers ◽  
Inflammatory Cells ◽  
Rimmed Vacuoles ◽  
Autophagic Vacuoles ◽  
Ultrastructural Evidence ◽  
Mitochondrial Defects

Abstract Context.—Bcl-2, Bcl-x, and Bax are among the variety of proteins that have been described as being involved in the regulation of apoptotic cell death. Bcl-2 and Bcl-xL inhibit apoptosis, and Bax is proapoptotic. Objective.—To evaluate the expression of Bcl-2, Bcl-x, and Bax in inclusion body myositis (IBM). Design.—We examined muscle specimens from 27 patients (17 men, 10 women) with IBM to evaluate Bcl-2, Bcl-x, and Bax expression by immunohistochemistry. Results.—Patient ages ranged from 29 to 80 years (mean 62.2 years). All biopsies were marked by endomysial chronic inflammation, muscle fiber necrosis, and regeneration. Rimmed (autophagic) vacuoles were present in all cases. Ragged red fibers were noted in 4 biopsies (15%), and cytochrome oxidase–deficient fibers were found in 10 biopsies (37%). Ultrastructural evidence of intranuclear or cytoplasmic tubulofilamentous inclusions, confirming the diagnosis of IBM, were noted in all cases. Paracrystalline mitochondrial inclusions were seen in 5 biopsies (18.5%). Inflammatory cells stained positively with Bcl-2 in all biopsies, Bax in 26 biopsies (96%), and Bcl-x in 8 biopsies (30%). Degenerating muscle fibers were highlighted with Bax in 24 biopsies (89%), Bcl-2 in 2 biopsies (7%), and Bcl-x in 3 biopsies (11%). Regenerative muscle fibers were noted to stain with Bax in 24 muscles (89%), Bcl-2 in 21 muscles (78%), and Bcl-x in 4 muscles (15%). Rimmed vacuoles were highlighted by Bax in 24 biopsies (89%) and only rarely by Bcl-2 (n = 2, 7%) and Bcl-x (n = 3, 11%). A subsarcolemmal staining pattern was observed in 21 biopsies (78%) with Bax, 6 biopsies (22%) with Bcl-2, and only 1 biopsy (4%) with Bcl-x. Conclusions.—(1) Bax (proapoptotic) immunostaining highlighted most autophagic vacuoles; (2) subsarcolemmal Bax and Bcl-2 immunoreactivity may be associated with mitochondrial defects that are commonly noted in IBM; (3) Bcl-2 and Bax immunoreactivity were not confined to degenerating muscle fibers and in fact appeared to be expressed more commonly in regenerating fibers, suggesting that their expression may be independent of apoptosis in the setting of IBM.

scholarly journals Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP)

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3487
Author(s):  
Shih-Ching Chang ◽  
Anna Fen-Yau Li ◽  
Pei-Ching Lin ◽  
Chun-Chi Lin ◽  
Hung-Hsin Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Gene Mutations ◽  
Proximal Colon ◽  
Tnm Stage ◽  
Cpg Island Methylator Phenotype ◽  
Kras Mutations ◽  
Methylator Phenotype ◽  
Next Generation Sequencing Ngs ◽  
Mutation Spectra

Background: The 5’-C-phosphate-G-3’ island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors. Methods: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patients after excluding five germline mismatch repair (MMR) gene mutations analyzed by next-generation sequencing (NGS) and confirmed by Sanger sequencing. The mutation spectra of 22 common CRC-associated genes were analyzed by NGS. Results: Of the 92 sporadic MSI-high tumors, 23 (25%) were considered CIMP-high (expressed more than 5 of 8 markers). CIMP-high tumors showed proximal colon preponderance and female predominance. The mutation profiles of CIMP-high tumors were significantly different from those of CIMP-low or CIMP-0 tumors (i.e., higher frequencies of BRAF, POLD1, MSH3, and SMAD4 mutations but lower frequencies of APC, TP53, and KRAS mutations). Multivariate analysis demonstrated that tumor, node, metastasis (TNM) stage was the independent prognostic factor affecting overall survival (OS). Among the MSI-high cases, the CIMP status did not impact the outcome of patients with MSI-high tumors. Conclusions: Only TNM stage was a statistically significant predictor of outcomes independent of CIMP profiles in MSI-high CRC patients. Sporadic MSI-high CRCs with different mechanisms of carcinogenesis have specific mutation profiles and clinicopathological features.

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