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Other Genetic (other + genetic)

Distribution by Scientific Domains
Medical Sciences50%
Life Sciences40%

Terms modified by Other Genetic

  • other genetic disorders
    		•

    Selected Abstracts

    Coexistence of Idiopathic Rolandic Epilepsy and CSWS in Two Families

    EPILEPSIA, Issue 10 2006
    Xavier De Tiège
    Summary:,Purpose: To report two families combining benign childhood epilepsy with centrotemporal spikes (BCECS) and cryptogenic epilepsy with continuous spike,waves during sleep (CSWS) in first-degree relatives. Methods: Clinical, EEG, and cerebral imaging data are described. Results: Family 1: The proband was 3 years old at epilepsy onset. First seizures were convulsive, with centrotemporal spikes on EEG. At age 5 years, he had complex partial seizures, psychomotor regression, and centrotemporal CSWS. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) showed left parietal hypermetabolism. After several antiepileptic drug (AED) trials, valproate (VPA) and ethosuximide (ESM) induced seizure remission, CSWS disappearance, and psychomotor improvement. Learning disabilities, however, persisted. Family history was remarkable for BCECS in his father. Family 2: The proband was 2 years old at epilepsy onset. First seizures were convulsive, with centrotemporal CSWS on EEG. Despite several AED trials including corticosteroids, focal negative myoclonia, atypical absences, and psychomotor regression occurred, leading to severe mental retardation. FDG-PET showed bilateral parietal hypermetabolism. Vagus nerve stimulator was implanted. Her family history was remarkable for BCECS in her father and febrile convulsions in infancy in her mother. Conclusions: These data suggest the existence of a common genetic basis between BCECS and cryptogenic epilepsies with CSWS. The higher expression in patients with CSWS could be related to other genetic or acquired factors. These data suggest that these epileptic syndromes constitute edges of a continuum. [source]

    Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia

    GENES, BRAIN AND BEHAVIOR, Issue 7 2007
    T. Karl
    Human genetic studies have shown that neuregulin 1 (NRG1) is a potential susceptibility gene for schizophrenia. Nrg1 influences various neurodevelopmental processes, which are potentially related to schizophrenia. The neurodevelopmental theory of schizophrenia suggests that interactions between genetic and environmental factors are responsible for biochemical alterations leading to schizophrenia. To investigate these interactions and to match experimental design with the pathophysiology of schizophrenia, we applied a comprehensive behavioural phenotyping strategy for motor activity, exploration and anxiety in a heterozygous Nrg1 transmembrane domain mutant mouse model (Nrg1 HET) using different housing conditions and age groups. We observed a locomotion- and exploration-related hyperactive phenotype in Nrg1 HETs. Increased age had a locomotion- and exploration-inhibiting effect, which was significantly attenuated in mutant mice. Environmental enrichment (EE) had a stimulating influence on locomotion and exploration. The impact of EE was more pronounced in Nrg1 hypomorphs. Our study also showed a moderate task-specific anxiolytic-like phenotype for Nrg1 HETs, which was influenced by external factors. The behavioural phenotype detected in heterozygous Nrg1 mutant mice is not specific to schizophrenia per se, but the increased sensitivity of mutant mice to exogenous factors is consistent with the pathophysiology of schizophrenia and the neurodevelopmental theory. Our findings reinforce the importance of carefully controlling experimental designs for external factors and of comprehensive, integrative phenotyping strategies. Thus, Nrg1 HETs may, in combination with other genetic and drug models, help to clarify pathophysiological mechanisms behind schizophrenia. [source]

    Molecular characterization of the role of orphan receptor small heterodimer partner in development of fatty liver,

    HEPATOLOGY, Issue 1 2007
    Jiansheng Huang
    The orphan receptor Small Heterodimer Partner (SHP, NROB2) regulates metabolic pathways, including hepatic bile acid, lipid, and glucose homeostasis. We reported that SHP- deletion in leptin-deficient OB,/, mice increases insulin sensitivity, and prevents the development of fatty liver. The prevention of steatosis in OB,/,/SHP,/, double mutants is not due to decreased body weight but is associated with increased hepatic very-low-density lipoprotein (VLDL) secretion and elevated microsomal triglyceride transfer protein (MTP) mRNA and protein levels. SHP represses the transactivation of the MTP promoter and the induction of MTP mRNA by LRH-1 in hepatocytes. Adenoviral overexpression of SHP inhibits MTP activity as well as VLDL-apoB protein secretion, and RNAi knockdown of SHP exhibits opposite effects. The expression of SHP in induced in fatty livers of OB,/, mice and other genetic or dietary models of steatosis, and acute overexpression of SHP by adenovirus, result in rapid accumulation of neutral lipids in hepatocytes. In addition, the pathways for hepatic lipid uptake and lipogenic program are also downregulated in OB,/,/SHP,/, mice, which may contribute to the decreased hepatic lipid content. Conclusion: These studies demonstrate that SHP regulates the development of fatty liver by modulating hepatic lipid export, uptake, and synthesis, and that the improved peripheral insulin sensitivity in OB,/,/SHP,/, mice is associated with decreased hepatic steatosis. (HEPATOLOGY 2007.) [source]

    Predictors of progression in patients with Friedreich ataxia,

    MOVEMENT DISORDERS, Issue 14 2008
    Alison La Pean MS
    Abstract Friedreich ataxia is an inherited, progressive, neurodegenerative disorder that is clinically heterogeneous. It is caused by a trinucleotide (GAA) repeat expansion resulting in frataxin loss and oxidative stress. We assessed clinical features including the development of cardiomyopathy and scoliosis and disease progression including loss of ambulation and interference with activities of daily living relative to the length of the GAA repeat, age of onset, and age of diagnosis in a retrospective cohort study of 61 genetically confirmed patients. The use of antioxidants such as vitamins, dietary supplements, and idebenone was also examined. Linear regression and Cox proportional hazard models assessed predictors to disease milestones. The shorter GAA allele accounted for part of the variability in the age of diagnosis (46%) and less in the age of onset (27%). Multivariate analysis demonstrated that age at diagnosis, which may incorporate other genetic and environmental factors, is more important than GAA length in predicting cardiomyopathy, scoliosis, and disease progression. © 2008 Movement Disorder Society [source]

    Deconstructing Jaco: Genetic Heritage of an Afrikaner

    ANNALS OF HUMAN GENETICS, Issue 5 2007
    J. M. Greeff
    Summary It is often assumed that Afrikaners stem from a small number of Dutch immigrants. As a result they should be genetically homogeneous, show founder effects and be rather inbred. By disentangling my own South African pedigree, that is on average 12 generations deep, I try to quantify the genetic heritage of an Afrikaner. As much as 6% of my genes have been contributed by slaves from Africa, Madagascar and India, and a woman from China. This figure compares well to other genetic and genealogical estimates. Seventy three percent of my lineages coalesce into common founders, and I am related in excess of 10 times to 20 founder ancestors (30 times to Willem Schalk van der Merwe). Significant founder effects are thus possible. The overrepresentation of certain founder ancestors is in part explained by the fact that they had more children. This is remarkable given that they lived more than 300 years (or 12 generations) ago. DECONSTRUCT, a new program for pedigree analysis, identified 125 common ancestors in my pedigree. However, these common ancestors are so distant from myself, paths of between 16 and 25 steps in length, that my inbreeding coefficient is not unusually high (f , 0.0019). [source]

    Transgenic mouse models of dopamine deficiency

    ANNALS OF NEUROLOGY, Issue S6 2003
    Linan Chen PhD
    The dopamine system is implicated in several neurological and psychiatric disorders. Genetic mutations or variations that affect dopamine system functions either directly cause or contribute to these disorders, even though other genetic and environmental factors may contribute significantly to some of these disorders as well. Transgenic mice increasingly become important tools in revealing functions of genes that are essential components of the dopamine system as well as in modeling human genetic disorders. We have reviewed a comprehensive list of those genes and compared genetic mutations/variations in humans and transgenic mouse models. The significance and limitations of these animal models as well as future directions are discussed. Ann Neurol 2003;54 (suppl 6):S91,S102 [source]

    Testing for Genetic Association in the Presence of Linkage and Gene,Covariate Interactions

    BIOMETRICAL JOURNAL, Issue 1 2010
    Andrea Callegaro
    Abstract In order to study family-based association in the presence of linkage, we extend a generalized linear mixed model proposed for genetic linkage analysis (Lebrec and van Houwelingen (2007), Human Heredity64, 5,15) by adding a genotypic effect to the mean. The corresponding score test is a weighted family-based association tests statistic, where the weight depends on the linkage effect and on other genetic and shared environmental effects. For testing of genetic association in the presence of gene,covariate interaction, we propose a linear regression method where the family-specific score statistic is regressed on family-specific covariates. Both statistics are straightforward to compute. Simulation results show that adjusting the weight for the within-family variance structure may be a powerful approach in the presence of environmental effects. The test statistic for genetic association in the presence of gene,covariate interaction improved the power for detecting association. For illustration, we analyze the rheumatoid arthritis data from GAW15. Adjusting for smoking and anti-cyclic citrullinated peptide increased the significance of the association with the DR locus. [source]

    MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinoma

    CELL BIOCHEMISTRY AND FUNCTION, Issue 6 2008
    Ivan Nisevic
    Abstract Chronic pancreatitis and pancreatic adenocarcinoma are extensively studied as common and potentially lethal disorders. However, their causes and genetic background in most cases remain unclear. The C677T polymorphism in 5,,10,-methylenetetrahydrofolate reductase (MTHFR) gene may modulate the risk of pancreatic disorders. In this study, we tested whether MTHFR C677T polymorphism is associated with chronic pancreatitis and pancreatic adenocarcinoma in the Serbian population. DNA was extracted from blood samples of 51 chronic pancreatitis patients, 21 pancreatic adenocarcinoma patients, and a control group consisting of 50 healthy smokers. The MTHFR C677T polymorphism was analyzed by polymerase chain reaction,restriction fragment length polymorphism (PCR,RFLP) technique. Although, no statistically significant differences were observed in the distribution of MTHFR genotype or allele frequencies between patients and control groups, the results showed an increased frequency of homozygotes for MTHFR C677T polymorphism in chronic pancreatitis patients (14%) and a decreased frequency in pancreatic adenocarcinoma patients (5%) in comparison to the control group (8%). We speculate that the MTHFR C677T polymorphism could act as a possible risk factor for chronic pancreatitis and a possible protective factor in pancreatic adenocarcinoma. This observation needs further investigation in prospective studies on a larger number of patients, in which the effect of other genetic and environmental factors should also be taken into consideration. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    Mutations within the transcription factor PROP1 are rare in a cohort of patients with sporadic combined pituitary hormone deficiency (CPHD)

    CLINICAL ENDOCRINOLOGY, Issue 1 2005
    James P. G. Turton
    Summary Objective, Mutations within the pituitary-specific paired-like homeobox gene PROP1 have been described in 50,100% of patients with familial combined pituitary hormone deficiency (CPHD). We screened a cohort of sporadic (n = 189) and familial (n = 44) patients with hypopituitarism (153 CPHD and 80 isolated hormone deficiencies) for mutations within the coding sequence of PROP1. Design and patients, Patients with congenital hypopituitarism were recruited from the London Centre for Paediatric Endocrinology as well as several national and international centres. The pituitary phenotype ranged from isolated growth hormone deficiency (IGHD) to panhypopituitarism. Clinical data, including endocrine and neuro-radiological studies were obtained from patient records, and DNA was collected and screened for mutations within PROP1 using PCR and single-stranded conformation polymorphism (SSCP) analysis. Positive results on SSCP were sequenced directly. Results, The prevalence of PROP1 mutations in unselected sporadic cases of hypopituitarism was lower (1·1%) than in familial cases (29·5%). PROP1 mutations can be associated with a highly variable phenotype, and both pituitary hypoplasia and pituitary hyperplasia. We describe the waxing and waning of a pituitary mass over 20 months in association with a PROP1 mutation that is predicted to lead to complete loss of function. Additionally, we have identified a possible founder mutation in CPHD patients from the Indian subcontinent. Conclusions,PROP1 mutations are rare in sporadic cases of CPHD, although the prevalence rises if there is a positive family history or if the patients are carefully selected with respect to the endocrine and neuroradiological phenotype. There is considerable phenotypic variability in families with the same mutation, indicating the role of other genetic or environmental factors on phenotypic expression. Finally, the pituitary enlargement that is observed in patients with PROP1 mutations can wax and wane in size before eventual involution. [source]

    Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis

    CLINICAL GENETICS, Issue 2 2010
    LE Almaguer-Mederos
    Almaguer-Mederosa LE, Falcón NS, Almira YR, Zaldivar YG, Almarales DC, Góngora EM, Herrera MP, Batallán KE, Armiñán RR, Manresa MV, Cruz GS, Laffita-Mesa J, Cyuz TM, Chang V, Auburger G, Gispert S, Pérez LV. Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis. Previous studies have investigated the close association that exists between CAG repeat number and the age at onset in SCA2 = spinocerebellar ataxia type 2. These studies have focused on affected individuals. To further characterize this association and estimate the risk of a carrier developing SCA2 at a particular age as a function of a specific CAG repeat size, we have analyzed a large group of 924 individuals, including 394 presymptomatic and 530 affected individuals with a CAG repeat length of 32,79 units. Using a Kaplan,Meier survival analysis, we obtained cumulative probability curves for disease manifestation at a particular age for each CAG repeat length in the 34,45 range. These curves were significantly different (p < 0.001) and showed small overlap. All these information may be very valuable in predictive-testing programs, in the planning of studies for the identification of other genetic and environmental factors as modifiers of age at onset, and in the design of clinical trials for people at enlarged risk for SCA2. [source]