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1.
Zhonghua Fu Chan Ke Za Zhi ; 55(9): 627-632, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32957751

RESUMO

Objective: To investigate the clinical characteristics and outcomes of monochorionic monoamniotic (MCMA) twin pregnancy. Methods: The clinical data of 60 MCMA twin pregnant women who were terminated in Peking University Third Hospital from January 2011 to December 2019 were collected, and the general clinical data, prenatal examination and pregnancy outcomes were analyzed retrospectively. Results: The age of 60 MCMA twin pregnant women was (31.0±4.1) years old, among which 44 cases were primiparas (73%, 44/60) and 16 cases were multiparas (27%, 16/60). Fifty-eight cases were diagnosed as MCMA twin pregnancy prenatally and were confirmed after delivery. Median ultrasonic diagnosis of gestational age was 12 weeks (range: 8-30 weeks). In the 60 MCMA twin pregnancies, 6 cases were conjoined twins, 5 cases were complicated with twin reversed arterial perfusion sequence (TRAPS), and 10 cases were diagnosed as other fetal malformation by prenatal ultrasound examination. Among the 60 MCMA twin pregnant women, 19 cases had spontaneous abortion or induced abortion due to fetal malformation, fetal death or other reasons within 28 weeks of pregnancy, 41 cases entered the perinatal period, a total of 70 newborns survived. The main cause of perinatal fetal or neonatal death was fetal dysplasia. Conclusions: There is a high incidence of fetal abnormality and perinatal mortality in MCMA twin pregnancy. Accurate early diagnosis, enhanced management and monitoring during pregnancy, and individualized treatment are the keys to improve MCMA twin pregnancy outcomes.


Assuntos
Âmnio/diagnóstico por imagem , Placenta/diagnóstico por imagem , Gravidez de Gêmeos , Gêmeos Monozigóticos , Ultrassonografia Pré-Natal/métodos , Adulto , Âmnio/fisiopatologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Mortalidade Perinatal , Placenta/fisiopatologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos
3.
BMC Surg ; 20(1): 181, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770973

RESUMO

BACKGROUND: To this date little information exists on the effects, clinical course and outcome of the COVID-19 among patients undergoing transplantation. CASE PRESENTATION: A 35 year old male referred with loss of sense of smell and taste after having close contact with his brother who was diagnosed with COVID-19 five days prior to his symptoms. The patient had undergone liver transplantation 3 years prior to his referral due to primary sclerosing cholangitis in association with ulcerative colitis and was using immunosuppressive medications. The patient referred to a local physician with mild symptoms of fatigue, cough, myalgia, dizziness, and nausea/vomiting with a fear of contracting the disease. Except for a CRP of 32 his other blood tests were normal. After 3 days of hospital admission the patient was discharged with a good condition. His brother had developed fever, chills, headache, mild dyspnea and an objective loss of sense of smell and taste and was sent home and advised to self-quarantine. Both patients had CT scans in favor of COVID-19. CONCLUSION: Our patient who had liver transplantation and COVID-19 did not present more severe symptoms compared to his counterpart without liver transplantation and did not need to be hospitalized or be given antiviral drugs for COVID-19.


Assuntos
Infecções por Coronavirus/fisiopatologia , Transplante de Fígado , Pneumonia Viral/fisiopatologia , Gêmeos Monozigóticos , Adulto , Cefaleia/virologia , Hospitalização , Humanos , Masculino , Pandemias , Tomografia Computadorizada por Raios X
4.
Pediatrics ; 146(Suppl 1): S33-S41, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32737230

RESUMO

Cases of adolescents in organ failure who refuse solid organ transplant are not common, but several have been discussed in the media in the United States and the United Kingdom. Using the framework developed by Buchanan and Brock for surrogate decision-making, I examine what role the adolescent should morally play when deciding about therapy for life-threatening conditions. I argue that the greater the efficacy of treatment, the less voice the adolescent (and the parent) should have. I then consider how refusals of highly effective transplant cases are similar to and different from refusals of other lifesaving therapies (eg, chemotherapy for leukemia), which is more commonly discussed in the media and medical literature. I examine whether organ scarcity and the need for lifelong immunosuppression justify differences in whether the state intervenes when an adolescent and his or her parents refuse a transplant. I argue that the state, as parens patriae, has an obligation to provide the social supports needed for a successful transplant and follow-up treatment plan, although family refusals may be permissible when the transplant is experimental or of low efficacy because of comorbidities or other factors. I conclude by discussing the need to limit media coverage of pediatric treatment refusals.


Assuntos
Temas Bioéticos , Meios de Comunicação de Massa/ética , Transplante de Órgãos/ética , Consentimento dos Pais/ética , Recusa do Paciente ao Tratamento/ética , Adolescente , Família , Feminino , Humanos , Consentimento Informado por Menores/ética , Consentimento Informado por Menores/legislação & jurisprudência , Masculino , Transplante de Órgãos/legislação & jurisprudência , Consentimento dos Pais/legislação & jurisprudência , Participação do Paciente , Patient Self-Determination Act , Ética Baseada em Princípios , Recusa do Paciente ao Tratamento/legislação & jurisprudência , Gêmeos Monozigóticos , Reino Unido , Estados Unidos
5.
Tokai J Exp Clin Med ; 45(2): 81-87, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32602106

RESUMO

OBJECTIVE: We assessed the clinical characteristics and perinatal outcome of disorders specific to monochorionic diamniotic (MD) twin pregnancies, focusing on twin-twin transfusion syndrome (TTTS) and related disorders, such as selective intrauterine growth restriction (sIUGR), inter-twin amniotic fluid discordance (AFD), and twin anemia polycythemia sequence (TAPS). METHODS: We retrospectively reviewed 69 cases of MD twin pregnancies delivered after 22 weeks at our institution from January 2009 to September 2013. RESULTS: TTTS occurred in 9 cases (13%). There was a total of 11 cases (16%) of MD twins with sIUGR in this period. One case developed TTTS. All 3 cases (4%) of AFD in this study developed TTTS or sIUGR. CONCLUSION: AFD should be recognized as predictors of TTTS or sIUGR. Further studies on TTTS-related disorders allow a more precise subgroup categorization that enables optimal management.


Assuntos
Transfusão Feto-Fetal , Resultado da Gravidez , Gravidez de Gêmeos , Adulto , Feminino , Retardo do Crescimento Fetal , Transfusão Feto-Fetal/epidemiologia , Humanos , Gravidez , Estudos Retrospectivos , Gêmeos Monozigóticos
6.
PLoS One ; 15(7): e0235860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645058

RESUMO

The Human Connectome Project (HCP) is a large structural and functional MRI dataset with a rich array of behavioral and genotypic measures, as well as a biologically verified family structure. This makes it a valuable resource for investigating questions about individual differences, including questions about heritability. While its MRI data have been analyzed extensively in this regard, to our knowledge a comprehensive estimation of the heritability of the behavioral dataset has never been conducted. Using a set of behavioral measures of personality, emotion and cognition, we show that it is possible to re-identify the same individual across two testing times (fingerprinting), and to identify identical twins significantly above chance. Standard heritability estimates of 37 behavioral measures were derived from twin correlations, and machine-learning models (univariate linear model, Ridge classifier and Random Forest model) were trained to classify monozygotic twins and dizygotic twins. Correlations between the standard heritability metric and each set of model weights ranged from 0.36 to 0.7, and questionnaire-based and task-based measures did not differ significantly in their heritability. We further explored the heritability of a smaller number of latent factors extracted from the 37 measures and repeated the heritability estimation; in this case, the correlations between the standard heritability and each set of model weights were lower, ranging from 0.05 to 0.43. One specific discrepancy arose for the general intelligence factor, which all models assigned high importance, but the standard heritability calculation did not. We present a thorough investigation of the heritabilities of the behavioral measures in the HCP as a resource for other investigators, and illustrate the utility of machine-learning methods for qualitative characterization of the differential heritability across diverse measures.


Assuntos
Conectoma , Imagem por Ressonância Magnética , Cognição , Conectoma/métodos , Emoções , Genótipo , Humanos , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Personalidade , Fenótipo , Gêmeos Monozigóticos
7.
J Oral Rehabil ; 47(9): 1110-1119, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32613647

RESUMO

BACKGROUND: Sleep bruxism (SB) and awake bruxism (AB) have been considered different entities, although co-occurrence between them has been shown. While genetic factors have a marked influence on phenotypic variance in liability to SB, this remains unclear for AB. AIM: To examine the degree of co-occurrence of SB and AB, and whether they have common correlates and also twin similarity of SB and AB bruxism traits by zygosity and sex. METHODS: A questionnaire was mailed to all twins born 1945-1957 in Finland in 2012 (n = 11 766). Age and sex adjusted logistic regression models were used. Twin similarity was assessed using polychoric correlations, and crosstwin-crosstrait correlations were computed. RESULTS: The response rate was 72% (n = 8410). Any SB was reported by 14.8% and ≥ 3 nights weekly by 5.0%. Percentages for any AB were 18.4% and 6.3%, respectively. There was substantial co-occurrence (29.5%) between SB and AB, and several shared correlates were found. For SB, the polychoric intra-class correlation was 0.366 in monozygotic (MZ) and 0.200 in dizygotic (DZ) pairs, without gender difference. A twofold crosstwin-crosstrait correlation was observed in MZ twins compared to DZ twins. CONCLUSIONS: The risk factor profiles of SB and AB were largely but not entirely similar. The higher correlation in MZ than in DZ pairs suggests the influence of genetic factors on both SB and AB. The higher crosstwin-crosstrait correlation in MZ than in DZ pairs suggests some degree of genetic influences shared by SB and AB.


Assuntos
Gêmeos Dizigóticos , Vigília , Finlândia , Humanos , Autorrelato , Gêmeos Monozigóticos
8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(3): 425-431, 2020 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-32541973

RESUMO

OBJECTIVE: To explore the cytidine-phosphate-guanosine (CPG) sites associated with fas-ting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in twins. METHODS: In the study, 169 pairs of monozygotic twins were recruited in Qingdao, Zhejiang, Jiangsu, Sichuan and Heilongjiang in June to December of 2013 and June 2017 to October 2018. The methylation was detected by Illumina Infinium HumanMethylation450 BeadChip and Illumina Infinium MethylationEPIC BeadChip. According to the Linear Mixed Effect model (LME model), fasting plasma glucose and HbA1c were taken as the main effects, the methylation level (ß value) was taken as the dependent variable, continuous variables, such as age, body mass index (BMI), blood pressure, components of blood cells, surrogate variables generated by SVA, and categorical variables, such as gender, smoking and drinking status, hypoglycemic drugs taking, were included in the fixed effect model as covariates, and the identity numbers (ID) of the twins was included in the random effect model. The intercept was set as a random. Regression analysis was carried out to find out the CpG sites related to fasting blood glucose or HbA1c, respectively. RESULTS: In this study, 338 monozygotic twins (169 pairs) were included, with 412 459 CpG loci. Among them, 114 pairs were male, and 55 pairs were female, with an average age of (48.2±11.9) years. After adjustment of age, gender, BMI, blood pressure, smoking, drinking, blood cell composition, and other covariates, and multiple comparison test, 7 CpG sites (cg19693031, cg01538969, cg08501915, cg04816311, ch.8.1820050F, cg06721411, cg26608667) were found related to fasting blood glucose, 3 of which (cg08501915, ch.8.1820050f, cg26608667) were the newly found sites in this study; whereas 10 CpG sites (cg19693031, cg04816311, cg01538969, cg01339781, cg01676795, cg24667115, cg09029192, cg20697417, ch.4.1528651F, cg16097041) were found related to HbA1c, and 4 of which(cg01339781, cg24667115, cg20697417, and ch.4.1528651f) were new. We found that cg19693031 in TXNIP gene was the lowest P-value site in the association analysis between DNA methylation and fas-ting plasma glucose and HbA1c (PFPG=2.42×10-19, FDRFPG<0.001; PHbA1c=1.72×10-19, FDRHbA1c<0.001). CONCLUSION: In this twin study, we found new CpG sites related to fasting blood glucose and HbA1c, and provided some clues that partly revealed the potential mechanism of blood glucose metabolism in terms of DNA methylation, but it needed further verification in external larger samples.


Assuntos
Metilação de DNA , Adulto , Glicemia , Ilhas de CpG , Epigênese Genética , Jejum , Feminino , Hemoglobina A Glicada , Humanos , Masculino , Pessoa de Meia-Idade , Gêmeos Monozigóticos
9.
Adv Exp Med Biol ; 1253: 95-104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32445092

RESUMO

Genomic predisposition fails to fully explain the onset of complex diseases, which is well illustrated by the largely incomplete concordance among monozygotic twins. Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and non-coding RNA, are the link between environmental stimuli and disease onset on a permissive genetic background in autoimmune and chronic inflammatory diseases. Autoimmune diseases now include almost 100 conditions and are estimated to cumulatively affect up to 5% of the world population with a healthcare expenditure superior to cancer worldwide. Many advances in medicine have been made to treat these conditions but there are still gaps, and an innovative and efficient therapy is needed. Systemic autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, polymyositis, and dermatomyositis. Monozygotic twins discordant for any disease offer an ideal study design as they are matched for many factors, including genetic variation and this is a real advantage for epigenetics study. We will herein discuss the available data in the epigenetic differences leading to disease discordance in MZ twins for systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis.


Assuntos
Epigênese Genética , Epigenômica/métodos , Estudos em Gêmeos como Assunto , Gêmeos Monozigóticos/genética , Doenças Autoimunes/genética , Metilação de DNA , Humanos , Inflamação/genética
10.
Am J Cardiol ; 127: 135-138, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32430163

RESUMO

A unique clinical circumstance involving middle-aged male identical twins with obstructive hypertrophic cardiomyopathy (HC) is reported. The concordance of morphologic (i.e., phenotype) findings and clinical course between the 2 patients is remarkable, including timing of the onset and progression of heart failure due to left ventricular outflow tract obstruction, frequency of paroxysmal atrial fibrillation and beneficial response to surgical myectomy and Cox-Maze IV procedure (performed 14 days apart). Histopathology of resected ventricular septal muscle showed identical hallmarks of HC including myocyte disorganization, small vessel disease, and myocardial fibrosis. A missense variant of the CRYAB gene was identified as potentially relevant to the pathogenesis of HC in the twins. Taken together, these observations support a powerful genetic determinant for the morphologic and clinical expression of HC, with little or no environmental influence.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Doenças em Gêmeos , Ecocardiografia/métodos , Função Ventricular Esquerda/fisiologia , Septo Interventricular/diagnóstico por imagem , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gêmeos Monozigóticos
11.
Ann Hematol ; 99(7): 1643-1653, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32458063

RESUMO

To explore the incidence, risk factors, and outcomes of central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and to compare the differences in CNS relapse between haploidentical donor HSCT (HID-HSCT) and HLA-identical sibling donor HSCT (ISD-HSCT). We performed a retrospective nested case-control study on patients with CNS relapse after allo-HSCT. The cumulative incidence of CNS relapse was 4.06% after allo-HSCT in ALL, with a significantly poor prognosis. The incidence was 3.91% and 5.36% in HID-HSCT and ISD-HSCT, respectively (p = .227). Among the patients with CNS relapse, the overall survival (OS) at 3 years was 56.2 ± 6.8% in the HID-HSCT subgroup and 76.9 ± 10.2% in the ISD-HSCT subgroup (p = .176). The 3-year cumulative incidence of systemic relapse was also comparable between the two subgroups (HID-HSCT, 40.6 ± 7.4%; ISD-HSCT, 13.3 ± 8.7%, respectively, p = .085). Younger age (p = .045), T-ALL (p = .035), hyperleukocytosis at diagnosis (p < .001), advanced disease stage at transplant (p < .001), pre-HSCT CNS involvement (p < .001), and absence of chronic graft vs host disease (cGVHD) (p < .001) were independent risk factors for CNS relapse after allo-HSCT. In conclusion, CNS relapse was a significant complication after allo-HSCT in ALL and was associated with poor prognosis. The incidences and outcomes were comparable between HID-HSCT and ISD-HSCT.


Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/secundário , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Irmãos , Transplante Haploidêntico , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/terapia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Teste de Histocompatibilidade/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Recidiva , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricos , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/estatística & dados numéricos , Resultado do Tratamento , Gêmeos Monozigóticos/estatística & dados numéricos , Adulto Jovem
12.
Eur J Endocrinol ; 182(5): 473-480, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32229696

RESUMO

Objective: Co-aggregation of autoimmune diseases is common, suggesting partly shared etiologies. Genetic factors are believed to be important, but objective measures of environmental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at estimating heritability and genetic overlap in seven organ-specific autoimmune diseases. Design: Prospective twin cohort study. Methods: We used a cohort of 110 814 twins to examine co-aggregation and heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 diabetes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disease as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estimate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using structural equational modeling adjusting for censoring and truncation of data. Results: Co-aggregation was more pronounced in monozygotic twins (median HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moderate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0.71) for Graves' disease to 0.97 (95% CI: 0.91-1.00) for Addison's disease. Conclusions: Overall, co-aggregation was more pronounced in monozygotic than in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co-aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our results validate and refine previous heritability estimates based on smaller twin cohorts.


Assuntos
Autoimunidade/fisiologia , Doença de Addison/genética , Autoimunidade/genética , Doença Celíaca/genética , Estudos de Coortes , Feminino , Gastrite Atrófica/genética , Predisposição Genética para Doença/genética , Doença de Graves/genética , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
13.
World Neurosurg ; 139: 286-288, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32247796

RESUMO

BACKGROUND: Intracranial fetus in fetu is an extremely rare entity in which a discrete vertebrate fetiform mass is found inside a diamniotic, monochorionic twin. It is a benign mass and can manifest with symptoms owing to mass effect. To establish the diagnosis, a vertebra must be present within the mass. CASE DESCRIPTION: A 5-year-old child presented at a multispecialty hospital with gradual weakness of both lower limbs. Magnetic resonance imaging of the brain revealed a midline intraventricular mass with lobulated margins having both cystic and fatty components with areas of blooming within. A provisional diagnosis of teratoma/primitive neuroectodermal tumor was made. The patient subsequently presented to our hospital with drowsiness and vomiting for 1 day. Noncontrast computed tomography revealed a mass of heterogeneous density occupying the third ventricle. The mass contained a few well-formed long bones representative of the appendicular skeleton and a vertebra-like bone representative of the axial skeleton, fulfilling the Willis criteria. A biopsy sample was taken from the mass; no malignant cells were seen on histopathologic examination. Based on noncontrast computed tomography findings of well-formed long bones and a vertebra and no significant increase in the size of the mass over 2 years, an intracranial fetus in fetu was diagnosed. CONCLUSIONS: Whenever bony structures are identified in an intracranial mass in a pediatric patient, we should always look for bones of the axial skeleton, as this finding will point toward a diagnosis of intracranial fetus in fetu and will help in differentiating it from teratoma, which can have malignant transformation.


Assuntos
Encéfalo/anormalidades , Feto/anormalidades , Pré-Escolar , Humanos , Masculino , Gêmeos Monozigóticos
14.
Arch Dis Child ; 105(9): 864-868, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32156695

RESUMO

OBJECTIVES: To assess evidence supporting the view that 'low fibre causes childhood constipation'. DESIGN: Triangulation integrated three approaches: a systematic review NICE guideline CG99 examining effectiveness of increasing fibre; a cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), to assess if constipation (or hard stools) can precede fibre intake at weaning; and a literature search for twin studies to calculate heredity. SETTING: CG99 examined the literature regarding the effectiveness of increasing fibre. ALSPAC asked parents about: hard stools at 4 weeks, 6 months and 2.5 years and constipation at age 4-10 years, as well as fibre intake at 2 years. Twin studies and data from ALSPAC were pooled to calculate concordance of constipation comparing monozygotic and dizygous twin pairs. PARTICIPANTS: CG99 reported six randomised controlled trials (RCTs). ALSPAC hard stool data from 6796 children at 4 weeks, 9828 at 6 months and 9452 at 2.5 years plus constipation data on 8401 at 4-10 years were compared with fibre intake at 2 years. Twin studies had 338 and 93 twin pairs and ALSPAC added a further 45. RESULTS: Increasing fibre did not effectively treat constipation. Hard stools at 4 weeks predated fibre and at 6 months predicted lower fibre intake at 2 years (p=0.003). Heredity explained 59% of constipation. CONCLUSIONS: RCTs indicate that increasing fibre is not an effective treatment for constipation in children. Hard stools can precede and predict later fibre intake. Genetic inheritance explains most childhood constipation. Extended treatment with stool softeners may improve fibre intake and limit long-term damaging sequelae of constipation.


Assuntos
Constipação Intestinal/etiologia , Fibras na Dieta/deficiência , Adolescente , Criança , Pré-Escolar , Constipação Intestinal/epidemiologia , Constipação Intestinal/genética , Fibras na Dieta/administração & dosagem , Doenças em Gêmeos/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Inquéritos e Questionários , Gêmeos Dizigóticos , Gêmeos Monozigóticos
15.
Gene ; 738: 144461, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32057927

RESUMO

Down syndrome is one of the most common chromosomal disorders and yet our understanding about the dysregulated genes in this disease is limited. Through this case study, we investigated the gene expression profile of primary amniotic fluid mesenchymal stem cells (AFMSCs) isolated from the amniotic sac of monozygotic twins discordant for trisomy 21 with one fetal hydrops at 17 weeks of gestation. AFMSCs were cultured to analyze the gene expression profiles for the human transcriptome array. Gene ontology was used to evaluate dysregulated gene functions. Total 25,799 genes were identified such that 65 were up-regulated (0.25%) and 111 were down-regulated (0.43%) with a log2 fold change trisomy 21/euploidy (log2 [FC]) > 1, p < 0.01). 16 genes were selected and verified by qRT-PCR, which showed compatible result with transcriptome array. At the chromosome level, chromosome 21 was found to carry the highest percentage of up-regulated genes (2.13%, 7/329 genes) with the highest mean log2 [FC] (0.23, p < 10-5), particularly on 21q22.3. There were eight segments with significant mean log2 [FC] on chromosomes 1, 6, 11, and 21 for upregulation, and on chromosomes 16, 17, and 19 for downregulation, indicating a pattern of dysregulated genes clustering in domains along the genome. Gene ontology showed the identified genes associated with extracellular matrix organization (11 genes, p = 5.1 × 10-6) and central nervous system development (8 genes, p = 6.0 × 10-5). Using transcriptome analysis of the AFMSCs of monozygotic twins discordant for trisomy 21, we report the dysregulated genes involved in Down syndrome, their predominance on chromosome 21, and the cluster pattern on the whole genome.


Assuntos
Síndrome de Down/genética , Perfilação da Expressão Gênica/métodos , Análise em Microsséries/métodos , Líquido Amniótico , Transtornos Cromossômicos/genética , Doenças em Gêmeos/genética , Feminino , Ontologia Genética , Genoma , Genótipo , Humanos , Células-Tronco Mesenquimais/fisiologia , Fenótipo , Gravidez , Transcriptoma/genética , Trissomia/genética , Gêmeos Monozigóticos/genética
16.
Nat Commun ; 11(1): 709, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024844

RESUMO

Human visual cortex contains discrete areas that respond selectively to specific object categories such as faces, bodies, and places. A long-standing question is whether these areas are shaped by genetic or environmental factors. To address this question, here we analyzed functional MRI data from an unprecedented number (n = 424) of monozygotic (MZ) and dizygotic (DZ) twins. Category-selective maps were more identical in MZ than DZ twins. Within each category-selective area, distinct subregions showed significant genetic influence. Structural MRI analysis revealed that the 'genetic voxels' were predominantly located in regions with higher cortical curvature (gyral crowns in face areas and sulcal fundi in place areas). Moreover, we found that cortex was thicker and more myelinated in genetic voxels of face areas, while it was thinner and less myelinated in genetic voxels of place areas. This double dissociation suggests a differential development of face and place areas in cerebral cortex.


Assuntos
Modelos Genéticos , Córtex Visual/diagnóstico por imagem , Córtex Visual/fisiologia , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Memória de Curto Prazo , Experimentação Humana não Terapêutica , Estimulação Luminosa , Gêmeos Dizigóticos , Gêmeos Monozigóticos
17.
Behav Genet ; 50(2): 127-138, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32040643

RESUMO

The univariate bootstrap is a relatively recently developed version of the bootstrap (Lee and Rodgers in Psychol Methods 3(1): 91, 1998). DeFries-Fulker (DF) analysis is a regression model used to estimate parameters in behavioral genetic models (DeFries and Fulker in Behav Genet 15(5): 467-473, 1985). It is appealing for its simplicity; however, it violates certain regression assumptions such as homogeneity of variance and independence of errors that make calculation of standard errors and confidence intervals problematic. Methods have been developed to account for these issues (Kohler and Rodgers in Behav Genet 31(2): 179-191, 2001), however the univariate bootstrap represents a unique means of doing so that is presaged by suggestions from previous DF research (e.g., Cherny et al. in Behav Genet 22(2): 153-162, 1992). In the present study we use simulations to examine the performance of the univariate bootstrap in the context of DF analysis. We compare a number of possible bootstrap schemes as well as more traditional confidence interval methods. We follow up with an empirical demonstration, applying results of the simulation to models estimated to investigate changes in body mass index in adults from the National Longitudinal Survey of Youth 1979 data.


Assuntos
Interpretação Estatística de Dados , Genética Comportamental/métodos , Modelos Estatísticos , Adolescente , Adulto , Índice de Massa Corporal , Peso Corporal/genética , Intervalos de Confiança , Feminino , Humanos , Estudos Longitudinais , Masculino , Modelos Genéticos , Fenótipo , Análise de Regressão , Meio Social , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto Jovem
18.
Psychiatr Genet ; 30(2): 60-63, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32106127

RESUMO

Whole-exome sequencing (WES) studies have shown that de-novo variants contribute to the genetic etiology of schizophrenia. WES studies of families with a monozygotic twin pair concordant or discordant for a disease may be fruitful for identifying de-novo pathogenic variants. Here, we performed WES in six individuals from one family (affected monozygotic twins, their unaffected parents, and two siblings) and identified three de-novo missense variants (CPT2 Ala283Thr, CPSF3 Val584Ile, and RNF148 Val210Ile) in the monozygotic twin pair concordant for schizophrenia. These three missense variants were not found in 1760 patients with schizophrenia or schizoaffective disorder or 1508 healthy controls. Our data do not support the role of the three missense variants in conferring risk for schizophrenia.


Assuntos
Transtornos Psicóticos/genética , Esquizofrenia/genética , Adulto , Carnitina O-Palmitoiltransferase/genética , Estudos de Casos e Controles , Fator de Especificidade de Clivagem e Poliadenilação/genética , Variações do Número de Cópias de DNA/genética , Exoma , Feminino , Seguimentos , Predisposição Genética para Doença/genética , Humanos , Masculino , Linhagem , Análise de Sequência de DNA , Irmãos , Gêmeos Monozigóticos/genética , Ubiquitina-Proteína Ligases/genética , Sequenciamento Completo do Exoma/métodos
19.
Brain ; 143(3): 920-931, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32025699

RESUMO

A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson's disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson's disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson's disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson's disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson's disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson's disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.


Assuntos
Imunoensaio/métodos , Doença de Parkinson/metabolismo , Pele/metabolismo , Sinucleínas/metabolismo , Gêmeos Monozigóticos/genética , Sistema Nervoso Autônomo/metabolismo , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Terminações Pré-Sinápticas/metabolismo
20.
Harefuah ; 159(1): 18-20, 2020 Jan.
Artigo em Hebraico | MEDLINE | ID: mdl-31930801

RESUMO

INTRODUCTION: Genetic twin studies may shed light on the genetic basis as well as environmental and epigenetic factors in disease pathogenesis. Herein, we present four pairs of monozygotic twins sharing similar phenotypes in three dermatologic conditions, and a literature review regarding twin studies in these diseases.


Assuntos
Dermatopatias , Gêmeos Monozigóticos , Humanos , Fenótipo
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