共查询到20条相似文献,搜索用时 15 毫秒
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J.A.N. Meester A. Verstraeten M. Alaerts D. Schepers L. Van Laer B.L. Loeys 《Clinical genetics》2019,95(1):85-94
The NOTCH signalling pathway is an essential pathway, involved in many cellular processes, including cell fate decision, cell proliferation, and cell death and important in the development of most organs. Mutations in genes encoding components of the NOTCH signalling pathway lead to a spectrum of congenital disorders. Over the past decades, mutations in human NOTCH signalling genes have been identified in several diseases with cardiovascular involvement. NOTCH1 mutations have been described in bicuspid aortic valve disease, left-sided congenital heart disease, and Adams-Oliver syndrome. NOTCH2 mutations lead to the development of Alagille syndrome, while mutations in NOTCH3 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. To date, mutations in NOTCH4 have not been associated with cardiovascular disease. This review focuses on the mutations described in NOTCH1, NOTCH2, and NOTCH3 and their associated cardiovascular phenotypes. 相似文献
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Maurizio Clementi Luisa Notari Adele Borghi Romano Tenconi 《American journal of medical genetics. Part A》1996,62(4):336-338
Congenital bicuspid aortic valve (BAV) is one of the most frequent heart defects detected by echocardiographic investigation and necropsy (0.9–1% of the general population), but only 16 families with familial congenital BAV have been described up to now. We report on a family in which 4 members of two generations (2 brothers, 1 sister, and her son) are affected with BAV. The BAV mode of inheritance is discussed. © 1996 Wiley-Liss, Inc. 相似文献
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目的 评价经胸超声心动图在诊断先天性主动脉瓣病变中的应用价值.方法 临床确诊的先天性主动脉瓣病变患者43例,其中男性25例,女性18例;年龄4~46岁,平均年龄234岁.纯合子家族性高胆固醇血症(HoFH)患者7例,主动脉瓣二叶畸形(BAV)患者35例,罕见的主动脉瓣下移畸形1例.回顾分析经胸超声心动图检查结果,并与彩... 相似文献
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N. D'ostrevy H. Ngo B. Magnin K. Azarnoush L. Cassagnes L. Camilleri 《Clinical anatomy (New York, N.Y.)》2018,31(5):693-697
Bicuspid aortic valves are associated with histopathological abnormalities of the aorta. Their diameters have been measured in several studies, but the literature concerning changes in the overall anatomy of the ascending aorta is limited. We wanted to know whether the anatomy of the valve, bicuspid or tricuspid, is associated with anatomical differences. We prospectively included patients requiring aortic valve surgery. The protocol included a chest CT scan before the operation to determine the angulations and straight lengths of aortic segments 0 and 1. All of the patients underwent surgery to assess their aortic valve morphology. We included 107 patients, 25 (23%) with bicuspid diagnostic valves and 82 (77%) with tricuspid ones. Most angulations were similar between the groups. However, the angle between the ring and the plane of the top of the commissures of the semilunar cusps was lower in bicuspid than tricuspid aortic valves. The straight lengths in the aortic root did not differ significantly, but the lengths separating these planes from the BCAT plane were consistently greater in the bicuspid group. The angle between the ring plane and the patient's vertical axis was lower in the bicuspid, the plane of the ring being verticalized in this group. In conclusion, we were able to confirm significant morphological differences in addition to the diameters. However, this study does not establish causal relationships among valve morphology, ascending aortic morphology, histology, and possibly associated pathologies. An extremely large cohort will be required indicate such causal connections. Clin. Anat. 31:693–697, 2018. © 2018 Wiley Periodicals, Inc. 相似文献
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J. Benes O. Dzupova M. Kabelkova P. Krizova A. Gabrielova 《Clinical microbiology and infection》2003,9(10):1062-1064
Two cases of meningococcal endocarditis are described. An 84-year-old man developed sepsis and septic shock and died 15 h after admission to the department. The autopsy revealed aortic endocarditis. Blood and vegetation culture yielded Neisseria meningitidis B:16:P1.5. A 37-year-old man was admitted for fever and rash lasting several weeks. Endocarditis of the bicuspid aortic valve caused by N. meningitidis C:2a:P1.2,5 was found. The patient was successfully treated with penicillin G for 4 weeks. Brief epidemiologic characteristics of invasive meningococcal disease in the Czech Republic are given. 相似文献
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Bruce D. Gelb Jian Zhang Robert J. Sommer Jared M. Wasserman Milton J. Reitman Judith P. Willner 《American journal of medical genetics. Part A》1999,87(2):175-179
The association between cardiac and limb defects, particularly those affecting the hand, has been well documented by the delineation of several heart-hand syndromes. Based on observations with a three-generation family with seven affected individuals, we describe a novel heart-hand syndrome comprising patent ductus arteriosus, bicuspid aortic valve, 5th metacarpal hypoplasia, and brachydactyly. The inheritance pattern was consistent with autosomal dominance, although X-linked dominance could not be excluded. Penetrance appeared to be complete, but there was variability of the cardiac and hand phenotypes. Because this new syndrome closely resembled Char syndrome (patent ductus arteriosus, 5th finger middle phalangeal hypoplasia, and minor facial anomalies), multipoint linkage analysis was performed using polymorphic DNA markers spanning the recently identified Char syndrome critical region at chromosomal bands 6p12–p21.1. This analysis formally excluded this 3-cM region, documenting that the two traits are not allelic. In sum, a novel heart-hand syndrome involving left ventricular outflow and aortic arch as well as an ulnar ray derivative has been identified. Because the hand anomalies can be subtle, thorough evaluation is suggested for families inheriting these cardiac defects as a mendelian trait. Am. J. Med. Genet. 87:175–179, 1999. © 1999 Wiley-Liss, Inc. 相似文献
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The analysis of cardiovascular malformations (CVM) in 3C (Ritscher-Schinzel) syndrome showed at least 9 types of CVM in 24 cases, including 4 cases from the Baltimore-Washington Infant Study. The proportion of different CVM forms was similar to that of the general population. The same is also true for many other syndromes of multiple congenital abnormalities (MCA), due either to aneuploidy or to Mendelian mutation. Such a wide spectrum of very different CVM in patients with the same entity has yet to be explained. According to the hypothesis proposed, the basic mutation (or chromosome imbalance) affects cellular homeostasis and leads to the “shifting” of a threshold to the left. This allows the expression of some genes silent under normal conditions. The principle of the shifted threshold is applicable to the explanation of the origin of many other defects in MCA syndromes. © 1996 Wiley-Liss, Inc. 相似文献
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Sans-Coma V Carmen Fernández M Fernández B Durán AC Anderson RH Arqué JM 《Journal of anatomy》2012,220(1):92-101
The bifoliate, or bicuspid, aortic valve (BAV) is the most frequent congenital cardiac anomaly in man. It is a heritable defect, but its mode of inheritance remains unclear. Previous studies in Syrian hamsters showed that BAVs with fusion of the right and left coronary leaflets are expressions of a trait, the variation of which takes the form of a phenotypic continuum. It ranges from a trifoliate valve with no fusion of the coronary leaflets to a bifoliate root devoid of any raphe. The intermediate stages are represented by trifoliate valves with fusion of the coronary aortic leaflets, and bifoliate valves with raphes. The aim of this study was to elucidate whether the distinct morphological variants rely on a common genotype, or on different genotypes. We examined the aortic valves from 1 849 Syrian hamsters belonging to a family subjected to systematic inbreeding by full-sib mating. The incidence of the different trifoliate aortic valve (TAV) and bifoliate aortic valve (BAV) morphological variants widely varied in the successive inbred generations. TAVs with extensive fusion of the leaflets, and BAVs, accounted for five-sixths of the patterns found in Syrian hamsters considered to be genetically alike or virtually isogenic, with the probability of homozygosity being 0.999 or higher. The remaining one-sixth hamsters had aortic valves with a tricuspid design, but in most cases the right and left coronary leaflets were slightly fused. Results of crosses between genetically alike hamsters, with the probability of homozygosity being 0.989 or higher, revealed no significant association between the valvar phenotypes in the parents and their offspring. Our findings are consistent with the notion that the BAVs of the Syrian hamster are expressions of a quantitative trait subject to polygenic inheritance. They suggest that the genotype of the virtually isogenic animals produced by systematic inbreeding greatly predisposes to the development of anomalous valves, be they bifoliate, or trifoliate with extensive fusion of the leaflets. We infer that the same underlying genotype may account for the whole range of valvar morphological variants, suggesting that factors other than genetic ones are acting during embryonic life, creating the so-called intangible variation or developmental noise, and playing an important role in the definitive anatomic configuration of the valve. The clinical implication from our study is that congenital aortic valves with a trifoliate design, but with fusion of coronary aortic leaflets, may harbour the same inherent risks as those already recognised for BAVs with fusion of right and left coronary leaflets. 相似文献
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The genetic basis of polycystic ovary syndrome 总被引:11,自引:3,他引:11
Franks S; Gharani N; Waterworth D; Batty S; White D; Williamson R; McCarthy M 《Human reproduction (Oxford, England)》1997,12(12):2641-2648
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women
of reproductive age. Familial clustering of cases suggests that genetic
factors play an important part in its aetiology. A number of studies of
families with several cases of PCOS have produced results suggesting an
autosomal dominant trait. Detailed analysis of a large number of affected
families has, however, cast some doubt about the mode of inheritance. An
autosomal dominant trait remains possible but a more complex aetiology
seems more likely. The results of our recent studies support the concept of
an oligogenic disorder in which genes affecting metabolic pathways in
glucose homeostasis and steroid biosynthesis are both involved. We review
evidence for an important role for the insulin gene minisatellite in the
aetiology of anovulatory PCOS and for the gene coding for P450 cholesterol
side chain cleavage (CYP11a) in the mechanism of excessive androgen
secretion in women with polycystic ovaries. We propose that the
heterogeneity of clinical and biochemical features in PCOS can be explained
by the interaction of a small number of key genes with environmental,
particularly nutritional, factors.
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Maria Delio Kathleen Pope Tao Wang Joy Samanich Chad R. Haldeman‐Englert Paige Kaplan Tamim H. Shaikh Jinlu Cai Robert W. Marion Bernice E. Morrow Melanie Babcock 《American journal of medical genetics. Part A》2013,161(3):527-533
Haploinsufficiency of the elastin gene (ELN) on 7q11.23 is responsible for supravalvular aortic stenosis (SVAS) and other arteriopathies in patients with Williams–Beuren syndrome (WBS). These defects occur with variable penetrance and expressivity, but the basis of this is unknown. To determine whether DNA variations in ELN could serve as genetic modifiers, we sequenced the 33 exons and immediately surrounding sequence of the ELN gene (9,455 bp of sequence) in 49 DNAs from patients with WBS and compared cardiovascular phenotypes. Four missense, and four novel intronic variants were identified from a total of 24 mostly intronic single nucleotide variations and one indel. Two missense changes were present in one patient each, one published, p.Gly610Ser in exon 27 (MAF, 0.003) and one novel, p.Cys714Tyr, in exon 33 (MAF, 0.001), were rare in the general population. To identify a statistical association between the variants identified here and cardiovascular phenotypes a larger cohort would be needed. © 2013 Wiley Periodicals, Inc. 相似文献
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Calloway TJ Martin LJ Zhang X Tandon A Benson DW Hinton RB 《American journal of medical genetics. Part A》2011,155(5):1015-1020
Bicuspid aortic valve (BAV) is the most common cardiovascular malformation and is a risk factor for aortic valve disease (AVD). AVD typically manifests later in life, and the majority of cases have BAV. The purpose of this study was to identify risk factors for AVD in individuals with BAV. Families enriched for BAV were identified in a pediatric population, and echocardiography was performed on all family members. AVD was identified as stenosis and/or insufficiency, and BAV morphology was defined as right–left (RL), right–non (RN) or indeterminate. Heritability (h2) of AVD and BAV morphology was estimated using variance components analysis (SOLAR). To assess AVD risk over time, we used Generalized Estimating Equations methodology (SAS) adjusting for age and gender. A total of 1,128 individuals from 226 families were evaluated. BAV was identified in 281 individuals (25%), and AVD was identified in 167 (59%) individuals with BAV. Previously, we identified a high heritability for BAV (h2 = 0.89 ± 0.06, P < 0.00001), but the heritability of AVD in the present study (0.07 ± 0.17, P = 0.33) was low. AVD was significantly associated with BAV morphology (P = 0.0027) and age (P = 0.0068). Children with RN BAV and adults with RL BAV were more likely to develop AVD. BAV is determined largely by genetic effects, but the phenotypic variability of AVD is primarily determined by nongenetic factors. BAV morphology may have predictive value for the time course of AVD. © 2011 Wiley‐Liss, Inc. 相似文献
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Minimally invasive approaches for aortic valve replacement are now at the forefront of pathological aortic valve treatment. New trials show comparability of these devices to existing therapies, not only in high-risk surgical cohorts but also in low-risk and intermediate-risk cohorts. This review provides vital clinical and anatomical background to aortic valvular disease treatment guidelines, while also providing an update on transcatheter aortic valve implantation (TAVI) devices in Europe, their interventional trials and associated complications. 相似文献
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Siddharth K. Prakash Carolyn A. Bondy Cheryl L. Maslen Michael Silberbach Angela E. Lin Laura Perrone Giuseppe Limongelli Hector I. Michelena Eduardo Bossone Rodolfo Citro BAVCon Investigators GenTAC Registry Investigators Scott A. Lemaire Simon C. Body Dianna M. Milewicz 《American journal of medical genetics. Part A》2016,170(12):3157-3164
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Shinichi Miyabara Masahiro Nakayama Kaoru Suzumori Nobuhisa Yonemitsu Hajime Sugihara 《American journal of medical genetics. Part A》1997,68(2):135-141
There have been few pathological investigations of 45,X embryos and fetuses from a developmental point of view. Since most 45,X embryos and fetuses are lost prenatally, it is important to investigate them morphologically in order to elucidate the pathogenesis of the abnormalities. In this study, 13 45,X fetuses with cervical cystic hygroma were examined between 12 and 23 weeks of pregnancy. Every case had a hypoplastic thymus. The aortic valve was bicuspid in 11 cases and unicuspid in 2 cases. The aortic arch showed tubular hypoplasia between the left carotid artery and the left subclavian artery in 12 cases and type B interruption in one case. Smooth muscle cells and elastic fibers were reduced in number in the hypoplastic aortic arch. These results suggest hypoplastic development of the fourth branchial arch. Combined abnormalities between the aortic arch and aortic valve are not infrequently observed in DiGeorge anomaly. A similar developmental mechanism apparently underlies the pathogenesis of 45,X embryos. Possible genes causing the abnormalities are discussed. Am. J. Med. Genet. 68:135–141, 1997 © Wiley-Liss, Inc. 相似文献
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Bernstein JA Bernstein D Hehr U Hudgins L 《American journal of medical genetics. Part A》2011,(9):2236-2241
We report on the clinical findings in siblings affected by the recently characterized X-linked form of hereditary cardiac valvular dystrophy or cardiac valve disease (OMIM 314400) due to mutations in the FLNA gene and review the literature on this condition. Although FLNA related cardiac valve disease is presumed to be a rare disorder, it is likely underdiagnosed. Several features of this condition may aid in its identification. FLNA related valvular disease can be recognized on the basis of its distinctive inheritance, early age of onset, and frequent multi-valve involvement. 相似文献
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Colleen M Pater Iris Gutmark‐Little Justin T Tretter Lisa J Martin Philippe Backeljauw Nicole M Brown 《American journal of medical genetics. Part A》2021,185(1):141-149
Turner syndrome is associated with an increased risk of aortic aneurysms and dissection. Recent 2017 clinical care guidelines recommend medical therapy to treat aortic dilatation, although whether this slows dilatation is unknown. We aimed to describe a pre‐guideline cohort of Turner syndrome patients with aortic dilatation, the rate of dilatation following diagnosis, and post therapy dilatation rates. We conducted a retrospective review of Turner syndrome patients with a dilated aortic root or ascending aorta by current definitions. In total, 40 patients were included with 22 treated patients. Most patients had 45,X karyotype, were white, non‐Hispanic, and received both growth hormone and estrogen. Except for hypertension, there were no differences in risk factors among treated and untreated groups. Bicuspid aortic valve was very common. Treatment group patients had significantly more dilated ascending aortas by absolute measurements and aortic size index. In an adjusted model, there was minimal change in aortic measures over time and this was not associated with medication use. In conclusion, in this cohort, Turner syndrome patients with aortic dilatation were more likely to be treated if they had hypertension and if they met multiple dilatation criteria. Further study is needed to establish medical therapy efficacy on dilatation progression. 相似文献