A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history

Objectives: Adenomatous polyposis of the colon is often secondary to an inherited mutation in adenomatous polyposis coli (APC) gene, however, approximately one third of patients have no family history of the disease. We studied the phenotype and genotype of adenomatous polyposis in patients without a family history. Methods: A cohort of 57 unrelated adenomatous polyposis patients were evaluated. Seventeen patients with no family history were compared with 40 patients who had a positive family history of the disease. Family history and medical records were collected and analyzed. Germline APC and Mut Y homologue (MYH) testing was undertaken. Results: Patients without a family history were diagnosed with polyposis at an older age (41 years vs. 32 years) and presenting more frequently with symptoms (76 vs 20, P < 0.05). The number of colonic polyps and frequency of extracolonic manifestation associated with adenomatous polyposis did not differ between the two groups. APC mutations were detected less frequently among patients without a family history of the disease (4 out of 17 vs 25 out of 40, P=0.007), even among those with greater than 100 colorectal adenomas (4 out of 12 versus 21 out of 29, P=0.03). One homozygous MYH mutation carrier (G382D) was detected among the six patients without a family history and without a germline APC mutation who were tested. Conclusions: Adenomatous polyposis patients without a family history are usually diagnosed with symptoms, and at a later age. Phenotypically, they are similar to those with a family history. However, germline APC mutations are detected far less frequently in patients without a family history. A small percentage of these cases may be secondary to biallelic germline MYH mutations.     

基于公共数据库分析CLDN10与MYH10在肾透明细胞癌中表达及预后的意义

目的 探讨CLDN10与MYH10在肾透明细胞癌中表达及预后的意义.方法 通过GEO数据库分析获取肾透明细胞差异基因,并使用DAVID数据库对差异基因进行富集分析和功能注释,通过HPA数据库获取CLDN10与MYH10在正常肾脏组织蛋白表达图谱,再通过GEPIA数据库获取CLDN10与MYH10表达差异及肾透明细胞癌患...     

Venous thromboembolism prophylaxis of a patient with MYH-9 related disease and COVID-19 infection: A case report

BACKGROUND The May-Hegglin anomaly is among a group of genetic disorders known as MYH9-related disease. Patients with inherited platelet disorders such as MayHegglin anomaly are at a variably increased risk for bleeding due to a combination of platelet dysfunction and thrombocytopenia. Patients admitted to the hospital with coronavirus disease 2019(COVID-19) infection are at an increased risk for a venous thromboembolism event(VTE). The National Institutes of Health COVID-19 treatment guidelines...     

Association between polymorphisms in non-muscle myosin heavy chain 9 gene and hypertension susceptibility in chronic kidney disease patients

Objective To explore the association between polymorphisms in non-muscle myosin heavy chain 9 gene (MYH9) and hypertension susceptibility in chronic kidney disease (CKD) patients. Methods Five hundred and ninety-five persons, including 301 patients with CKD and 294 healthy controls, were enrolled in the study. Two single nucleotide polymorphisms (SNPs) (rs3752462, rs4821480)were genotyped by TaqMan assay or a restriction fragment length polymorphism assay for a further case-control study. The discrepancies of the patients'quantitive traits (including age, sex, systolic and diastolic blood pressure, frequency of different primary diseases and using different kinds of antihypertensive drugs) among different genotypes of the two MYH9 SNPs were analyzed. Meanwhile,theassociation between polymorphisms in MYH9 and hypertension susceptibility in CKD patients were analyzed in the rs3752462 site. Results The systolic blood pressure of CT genotype patients[(147.94±27.40) mm Hg] was significantly higher than that of CC genotype patients [(136.43±19.09) mm Hg] by single factor analysis of variance (P＜0.05). The frequency of using all kinds of antihypertensive drugs for CC genotype patients (7.4%) was lower than that of TT (43.9%) and CT (48.7%) genotype patients (P＜0.05).After correcting the age factor, the result of Logistic regression analysis showed that CC genotype was a protective factor of systolic blood pressure increasing. The probability of high blood pressure for CT genotype patients with CKD was 0.175 times than that of CC genotype (95% CI 0.071,0.431). Conclusions The CKD patients who carry the rs3752462 site CC genotype of MYH9 gene are not prone to high blood pressure. Polymorphism of MYH9 gene rs3752462 site is associated with systolic blood pressure in CKD patients. It may indicate that allele C mutation for T can lead to the increase in systolic blood pressure.     

Arecoline inhibits myogenic differentiation of C2C12 myoblasts by reducing STAT3 phosphorylation

Areca nut (Areca catechu) is chewed regularly as a medical and psychoactive food by about 10% of the world population, in countries including India, Taiwan and parts of Southern Asia. Areca nut chewing during pregnancy has been associated with both lower birth weight and premature birth. Animals of low birth weights showed retardation of muscle development. Our previous study showed that arecoline, the major areca alkaloid, decreased the number of implanted embryos. Here we sought to determine the effects of arecoline in myogenic differentiation by in vitro assays using C2C12 myoblast cells. The results showed that arecoline higher than 0.4 mM significantly increased apoptosis and decreased viability of C2C12 cells. Morphometric measurements of myotube formation and analyses of myogenic markers, myosin heavy chain and myogenin, revealed that myogenic differentiation was inhibited by 0.04–0.08 mM arecoline. Moreover, phosphorylated but not total STAT3 was significantly inhibited by arecoline during myotube formation. These results indicate that arecoline inhibits the myogenic differentiation of C2C12 cells by reducing the activation of STAT3, an upstream regulator of myogenesis. Improved understanding of the effects of arecoline during myogenic differentiation may help to establish public health policies and to develop potential treatments for such patients.     

Novel Mutations Widen the Phenotypic Spectrum of Slow Skeletal/β‐Cardiac Myosin (MYH7) Distal Myopathy

Laing early onset distal myopathy and myosin storage myopathy are caused by mutations of slow skeletal/β‐cardiac myosin heavy chain encoded by the gene MYH7, as is a common form of familial hypertrophic/dilated cardiomyopathy. The mechanisms by which different phenotypes are produced by mutations in MYH7, even in the same region of the gene, are not known. To explore the clinical spectrum and pathobiology, we screened the MYH7 gene in 88 patients from 21 previously unpublished families presenting with distal or generalized skeletal muscle weakness, with or without cardiac involvement. Twelve novel mutations have been identified in thirteen families. In one of these families, the father of the proband was found to be a mosaic for the MYH7 mutation. In eight cases, de novo mutation appeared to have occurred, which was proven in four. The presenting complaint was footdrop, sometimes leading to delayed walking or tripping, in members of 17 families (81%), with other presentations including cardiomyopathy in infancy, generalized floppiness, and scoliosis. Cardiac involvement as well as skeletal muscle weakness was identified in nine of 21 families. Spinal involvement such as scoliosis or rigidity was identified in 12 (57%). This report widens the clinical and pathological phenotypes, and the genetics of MYH7 mutations leading to skeletal muscle diseases.