scholarly journals Identification of Three FBN1 Mutations in Chinese Patients with Typical or Incomplete Marfan Syndrome by Whole-Exome Sequencing

2020 ◽  
Vol 5 (1) ◽  
pp. 19-26
Author(s):  
Guangming Fang ◽  
Jinxin Miao ◽  
Ying Peng ◽  
Yafei Zhai ◽  
Chuchu Wang ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Novel Mutation ◽  
Family Members ◽  
Chinese Patients ◽  
Chinese Families ◽  
Whole Exome ◽  
The Family ◽  
Functional Consequences ◽  
The Relationship ◽  
Generation Sequencing

Objective: The purpose of this work was to obtain the phenotypes and detect potential mutations in three Chinese patients with Marfan syndrome (MFS) or incomplete MFS phenotypes.Methods: Three unrelated patients with a definite or suspected clinical diagnosis of MFS and their family members were recruited for research. Genomic DNA was extracted from peripheral blood of these patients and their family members. All the exons were sequenced by next-generation sequencing and the variants were further validated by Sanger sequencing. The functional consequences of the mutations were analyzed with various genomic resources and bioinformatics tools.Results: Three FBN1 mutations were identified in the three patients, including one novel mutation (2125G > A) and two previously reported mutations (4786C > T and 6325C > T). It was interesting to note that the parents of these patients were normal as assessed by clinical features or genetic testing, but all these mutations were detected in their offspring, except for the variant 6325C > T. We also found that a few young members of the family of probands (proband 1 and proband 2) have exhibited no manifestations of MFS so far, although they carry the same disease-causing mutation.Conclusions: We found three FBN1 mutations in three unrelated Chinese families with MFS by genome sequencing, and the relationship between genotypes and phenotypes in MFS patients needs further exploration.

Abstract 484: Mir-19b-3p Regulates Autophagy by Targeting Raf-1 During Hypertrophic Cardiomyopathy

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Anupam Mittal ◽  
Perundurai S Dhandapany
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Novel Mutation ◽  
Family Members ◽  
Large Family ◽  
Untranslated Regions ◽  
Whole Exome ◽  
Signaling Axis ◽  
Functional Consequences ◽  
Sarcomeric Genes

Hypertrophic cardiomyopathy (HCM) is a heterogenous disease predominantly caused by sarcomeric genes. However, 40-50% cases etiology are not known. RAF1 mutations cause syndromic and isolated childhood cardiomyopathies. Functional mutations in untranslated regions (UTRs) of RAF-1 gene are rare, and their role in cardiomyopathy is unexplored. UTRs are important sites for interaction of epigenetic regulators such as microRNAs (miR). miRs have exhibited as crucial regulators of the cardiac remodeling process. We identified a novel mutation in RAF-1 3’-UTR (an important site for binding of miR-19a-3p/19b-3p) in large family members associated with HCM. Whole exome sequencing revealed that these family members are negative for mutations in known cardiomyopathy associated genes. miR-19a/b are known to play a crucial role in cardiac hypertrophy. The aim of this study is to determine the role of miR-19a-3p/19b-3p in regulating RAF-1 expression and delineating the molecular and functional consequences of identified RAF-1 3’-UTR mutation. Our results show that the overexpression of miR-19b-3p, leads to downregulation of RAF-1 expression and regulation. Notably, miR-19b-3p was found to be pro-hypertrophic as its overexpression resulted in increasing hypertrophic markers including ANP and β-MHC expression. Moreover, findings from experiments using RAF1 +/+ and RAF1 -/- mouse embryo fibroblasts (MEFs) confirms the role of miR-19b-3p interaction and regulation of RAF-1 signaling axis. Interestingly, we also observed many autophagy markers (Atg3, Atg 12-5 complex, and LC3 II) are dysregulated by miR-19-b-3p overexpression. Our study uncovers a novel mechanism through which miR-19b-3p regulates autophagy by targeting RAF-1.

Family succession, professionalization and internationalization: a study of Brazilian family businesses

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Augusto Dalmoro Costa ◽  
Aurora Carneiro Zen ◽  
Everson dos Santos Spindler
Keyword(s):  
Family Business ◽  
Family Members ◽  
Secondary Data ◽  
Family Businesses ◽  
Three Dimensions ◽  
Content Type ◽  
The Family ◽  
Two Generations ◽  
Internationalization Strategies ◽  
The Relationship

PurposeThe purpose of this paper is to investigate the relationship between family succession, professionalization and internationalization in family businesses within the Brazilian context.Design/methodology/approachThe paper presents a multiple-case study method with three Brazilian family businesses that have at least two generations of the owning family involved in the business and an international presence of at least three years. In-depth interviews and secondary data were undertaken with family and non-family members of each case.FindingsThe authors' results show that a family business can boost its internationalization by introducing both succession planning and professionalization on international activities. As family members tend to be more risk-averse and focused on keeping the family business within the family, professionalization is a way of improving the firm's ability to expand internationally. This process tends to lead to lower performance by the firm for the first few months or the first year after the investment, but afterward, international performance tends to grow exponentially.Originality/valueOnly a few studies have been concerned on the relationship of these three dimensions. Thus, the research takes into account that professionalization and succession lead family businesses to improve their internationalization strategies.

scholarly journals Dialects Among Young Italian-Australians: A Shift in Attitude and Perception

2017 ◽  
Vol 52 (4) ◽  
pp. 467-483 ◽  
Author(s):  
Ruben Benatti ◽  
Angela Tiziana Tarantini
Keyword(s):  
Second Language ◽  
Social Identity ◽  
Heritage Language ◽  
Family Members ◽  
Third Generation ◽  
Instrumental Function ◽  
Self Evaluation ◽  
The Family ◽  
The Relationship ◽  
Italian Dialects

Abstract The aim of this article is to analyse the relationship that second- and third-generation Italian migrants in Australia have with the Italian dialect of their family. We report on the survey we recently carried out among young Italian-Australians, mainly learners of Italian as a second language. First, we analyse the motivation behind learning Italian as a heritage language. We then move on to describe their self-evaluation of their competence in the dialect of their family, and their perception thereof. Surprisingly, our survey reveals that not only are Italian dialects still understood by most second- and third-generation Italians (contrary to what people may think), but Italian dialects are also perceived by young Italian-Australians as an important part of their identity. For them, dialect is the language of the family, particularly in relation to the older members. It fulfills an instrumental function, as it enables communication with some family members who master neither English nor Italian, but above all, it is functional to the construction of their self and their social identity.

scholarly journals Den uhelbredeligt hjemløse kinesiske dagbogsfiktion

2021 ◽  
Vol 49 (131) ◽  
pp. 213-238
Author(s):  
Bo Ærenlund Sørensen
Keyword(s):  
Short Stories ◽  
Family Structure ◽  
Family Members ◽  
Boundary Crossing ◽  
Strict Scrutiny ◽  
Financial Costs ◽  
The Family ◽  
Social Importance ◽  
The Relationship

This article examines the disease motif in Lu Xun’s “Diary of a Madman” (1918) and in Ding Ling’s “Miss Sophia’s Diary” (1928) in their historical and medical contexts. At its most fundamental, the contemporaneous Chinese conception of health was thermodynamic, vesting the utmost importance in the circulation of energies and substances. This conception had immense social importance because it provided part of the ideological scaffolding for the family structure. Inside the family, established responsibilities and hierarchies purportedly served to guide this circulation in ways supportive of health, and the same considerations charged family members with maintaining strict scrutiny of the family’s barriers against any potentially illness-inducing influences that might penetrate the family fortress. Written at a time when political, social, and scientific verities were crumbling in China, these diaries record the foibles and concerns of two diseased individuals who stand alienated from their families and their immediate surroundings. By focusing on this alienation, as well as on the shared interests of the diarists in boundary crossing flows and anthropophagy, this article suggests that these short stories can profitably be read as explorations of the anxieties facing this generation of young Chinese as they sought to make a world for themselves independently of their families. What these stories dramatize is that leaving the family behind might have medical ramifications in addition to social and financial costs. In the current covid-19 context, we may not need reminding that ideas about disease and health relate in important ways to how we think of the relationship between families, boundaries, and vulnerability. 

scholarly journals Targeted Next-Generation Sequencing Identifies ABCA4 Mutations in Chinese Families with Childhood-Onset and Adult-Onset Stargardt Disease

2021 ◽  
Author(s):  
Ling-hui Qu ◽  
Xin Jin ◽  
Chao Zeng ◽  
Nian-gou Zhou ◽  
Yan-hong Liu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Chinese Patients ◽  
Macular Dystrophy ◽  
Adult Onset ◽  
Next Generation ◽  
Childhood Onset ◽  
Stargardt Disease ◽  
Chinese Families ◽  
Generation Sequencing

Background: Stargardt disease (STGD) is the most common form of juvenile macular dystrophy associated with progressive central vision loss, and is agenetically and clinically heterogeneous disease. Molecular diagnosis is of great significance in aiding the clinical diagnosis, helping to determine the phenotypic severity and visual prognosis. In this study, we determined the clinical and genetic features of seven childhood-onset and three adult-onset Chinese STGD families. We performed capture next generation sequencing (NGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes.  Methods: In all, 10unrelated Chinese families were enrolled. Panel based NGS was performed to identify potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes, including the five known STGD genes (ABCA4, PROM1, PRPH2, VMD2 and ELOVL4). Variant analysis, Sanger validation, and segregation tests were utilized to validate the disease-causing mutations inthese families. Results: Using systematic data analysis with an established bioinformatics pipeline and segregation analysis, 17 pathogenic mutations in ABCA4 were identified in the ten STGD families. Four of these mutations were novel: c.371delG, c.681T > G, c.5509C > T and EX37del. Childhood-onset STGD was associated with severe visual loss, generalized retinal dysfunction and was due to more severe variants in ABCA4 than those found in adult-onset disease. Conclusions: We expand the existing spectrum of STGD and reveal the genotype-phenotype relationships of the ABCA4 mutations in Chinese patients. Childhood-onset STGD lies at the severe end of the spectrum of ABCA4-associated retinal phenotypes.

scholarly journals Lisle Spouses: Business Partners or «Loving Friends»?

2020 ◽  
Vol 20 (4) ◽  
pp. 504-512
Author(s):  
Darya A. Kotlukova ◽  
Keyword(s):  
Family Members ◽  
Financial Situation ◽  
Business Partners ◽  
The Family ◽  
Court Life ◽  
Relationship Of ◽  
The Relationship

The article discusses the relationship of spouses in the early Tudors aristocratic family. The material from the correspondence of Lady Honour Lisle and Sir Arthur, Viscount Lisle, reveals topics that were discussed between spouses. These are business issues related to the financial situation of the family, news about family members, acquaintances and court life, exchange of gifts. The letters also show the feelings that the Lisle spouses had for each other. The author concludes that, despite differences in origin, behavior and characters, the Lord and Lady Lisle were not only business partners, but their relationships was based on respect, sincere affection, and, possibly, love.

scholarly journals Identification of NF1 Frameshift Variants in Two Chinese Families With Neurofibromatosis Type 1 and Early-Onset Hypertension

2021 ◽  
Vol 9 ◽  
Author(s):  
Yi-Ting Lu ◽  
Di Zhang ◽  
Xin-Chang Liu ◽  
Qiong-Yu Zhang ◽  
Xue-Qi Dong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Neurofibromatosis Type 1 ◽  
Early Onset ◽  
Family Members ◽  
Neurofibromatosis Type ◽  
Chinese Families ◽  
Whole Exome

Background: Neurofibromatosis type 1 (NF-1) is a common autosomal dominant disorder caused by mutations in the NF1 gene. It is characterized by multiple café-au-lait macules, cutaneous neurofibromas, optic glioma, Lisch nodules, and axillary and inguinal freckling. The aim of this study was to investigate NF1 mutations in two Chinese families with NF-1 who presented with early-onset hypertension, and to determine the prevalence of hypertension associated with NF-1 to better understand this complication.Methods: Whole-exome sequencing was performed for the probands with NF-1 from two unrelated families. Possible pathogenic mutation was predicted by bioinformatic tools. Sanger sequencing was used to confirm candidate variants in all available individuals for familial co-segregation analysis. We also performed a systematic literature review of studies that reported the prevalence of hypertension in patients with NF-1.Results: In family 1, a recurrent mutation c.6789_6792delTTAC in NF1 was identified in the proband but in no other family members, indicating that this is a de novo mutation. In family 2, a novel mutation c.6934_6936delGCAinsTGCT in NF1 was detected in the proband and two other family members, which co-segregated with the disease phenotype within the family. Both mutations were predicted to be pathogenic by bioinformatic analysis. We found hypertension was a relatively common complication of NF-1, with a prevalence range of 6.1–23.4%. Ambulatory blood pressure monitoring is a stable method for detecting initial alterations of the blood pressure pattern, particularly for pre-hypertension.Conclusions: We identified one recurrent (c.6789_6792delTTAC) and one novel frame-shift mutation (c.6934_6936delGCAinsTGCT) in two unrelated families with NF-1 using whole-exome sequencing. In consideration of phenotypic heterogeneity in NF-1, genetic testing is a robust tool which helps early and accurate diagnosis. Because hypertension is not a rare complication of NF-1, routine screening for hypertension in patients with NF-1, especially children and adolescents, is important to avoid serious cardiovascular events.

Attitudes of Owner-Managers' Children towards Family and Business Issues

2002 ◽  
Vol 26 (3) ◽  
pp. 5-19 ◽  
Author(s):  
Sue Birley
Keyword(s):  
Family Business ◽  
Family Members ◽  
Halo Effect ◽  
The Family ◽  
The Relationship

This paper reports responses from 412 children of owner-managers (61% sons and 39% daughters) with regard to their attitudes to family and business Issues. The assumption in the study was that respondents would display a consistent set of attitudes toward the relationship between the family and the business. For example, those who believed that “management successors should be chosen from the family” would also consider “the business (to be) stronger with family members involved.” Moreover, this group would view their parents’ business as a family business and would have joined or intend to join. The reverse would also apply. In other words, those who did not believe that “management successors should be chosen from the family” would nor view their parents’ business as a family business, and would have no intention to join. In the study, two distinct clusters of attitude were identified and were labelled the Family in and Family Out groups. While those in the Family in group were more likely to consider the business to be a family business, the results for the Family Out group were more complicated. The relationship held for those currently working in the business—the halo effect—but not for the rest. In other words, it was quite possible to belong to the Family in group and to see the business as a family business but not to have joined.

scholarly journals Diagnosis of Joubert Syndrome 10 in a Fetus with Suspected Dandy-Walker Variant by WES: A Novel Splicing Mutation in OFD1

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Siyuan Linpeng ◽  
Jing Liu ◽  
Jianyan Pan ◽  
Yingxi Cao ◽  
Yanling Teng ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Joubert Syndrome ◽  
Splicing Mutation ◽  
The Novel ◽  
Rt Pcr ◽  
Abnormal Karyotype ◽  
Whole Exome ◽  
The Family ◽  
Sequencing Result

Joubert syndrome (JBTS) is a clinically and genetically heterogeneous group of ciliary diseases. To date, 34 subtypes of JBTS have been classified due to different causative genes or extra clinical features. Most of them are autosomal recessive, while only the subtype 10 (JBTS10) is a quite rare X-linked recessive disorder caused by OFD1 mutations with few reports. In this study, by using whole exome sequencing (WES), a novel OFD1 splicing mutation (c.2488+2T>C) was identified in a male fetus with suspected Dandy-Walker variant (DWV) and syndactyly, for whom abnormal karyotype and pathogenic CNV have been excluded. This mutation was inherited from the mother who has experienced two similar pregnancies before. An abnormal skipping of exon 18 in OFD1 mRNA was confirmed by RT-PCR and sequencing. Result from quantitative RT-PCR also showed that total OFD1 mRNA in the index fetus was significantly lower than the control. After a combined analysis of genetic testing results and genotype-phenotype correlations, the novel mutation c.2488+2T>C in OFD1 was considered to be the genetic cause for the affected fetus. Thus the diagnosis should be JBTS10 rather than the primary clinical diagnosis of DWV. We report the first prenatal case of JBTS10 in Chinese population, which not only helps the family to predict recurrence risks for future pregnancies but also provides more information for understanding such a rare disease. The results also present evidence that WES is an effective method in prenatal diagnosis for those fetuses with Joubert syndrome.

Sign in / Sign up

Export Citation Format

Share Document