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Dominant Disease (dominant + disease)
Kinds of Dominant Disease Selected AbstractsAltered striatal amino acid neurotransmitter release monitored using microdialysis in R6/1 Huntington transgenic miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001B. NicNiocaill Abstract Huntington's disease is an autosomal dominant disease which presents with striatal and cortical degeneration causing involuntary movements, dementia and emotional changes. We employed 16-week-old transgenic Huntington mice (R6/1 line developed by Bates and coworkers) that express exon 1 of the mutant human Huntington gene with 115 CAG triplet repeats. At this age, R6/1 mice do not exhibit an overt neurological phenotype nor any striatal neuronal loss. Using microdialysis, we monitored basal and intrastriatal N-methyl d -aspartate (NMDA, 100 µm, 15 min)- and KCl (100 mm, 15 min)-induced increases in local aspartate, glutamate and GABA release in halothane-anaesthetized transgenic mice and wild-type controls. Basal striatal dialysate glutamate levels were reduced by 42% in R6/1 mice whilst aspartate and GABA levels did not differ from those observed in control mice. Intrastriatal NMDA was associated with significantly greater aspartate (at 15 min) and GABA (at 30 min) levels in the R6/1 mice compared to controls, whilst glutamate release rapidly increased to the same extent in both groups. Intrastriatal KCl was associated with enhanced increases (30 min) in local aspartate and glutamate release in the R6/1 mice above those observed in controls whilst the rapid increase (15 min) in GABA release was similar in both groups. The results provide compelling evidence for specific alterations in both basal, as well as NMDA- and KCl-induced, release of striatal amino acid neurotransmitters in this transgenic model of Huntington's disease, even in the absence of manifest neurodegeneration. [source] Keratin 9 gene mutations in five Korean families with epidermolytic palmoplantar keratodermaEXPERIMENTAL DERMATOLOGY, Issue 6 2003Joo-Heung Lee Abstract:, Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disease characterized clinically by localized palmoplantar thickening and histopathologically by granular degeneration of the epidermis. Recent molecular biological studies have revealed that EPPK is caused by mutations of the keratin 9 gene in sequences mainly encoding the highly conserved 1 A rod domain. Here we demonstrate a novel mutation of N160H (position 8 of the 1 A domain) and two other previously reported mutations, R162W and N160S, in five unrelated Korean families with EPPK. The three-dimensional structure of the 1 A domain of the related vimentin intermediate filament protein chain is now known. Based on its likely similarity to the keratin 9 chain, we predict that inappropriate amino acid substitutions in position 10 of 1 A will likely interfere with coiled-coil dimer stability, and those in position 8 will interfere with tetramer stability. Accordingly, these mutations compromise the structural integrity of the keratin intermediate filaments leading to the pathology of EPPK. [source] Fatal malignant melanoma in a child with neurofibromatosis type 1INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2007Yousef Bin Amer MBBS Neurofibromatosis type 1 is an autosomal dominant disease and is considered one of the most commonly inherited diseases in humans. Malignant melanoma has been reported in up to 5% of patients with neurofibromatosis type 1. We report a young Saudi boy with neurofibromatosis type 1 who developed fatal metastatic malignant melanoma arising from giant melanocytic nevi within speckled lentiginous nevus (SLN). [source] Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational eventINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2005Nicole L. Lacz MD Epidermolytic hyperkeratosis is an unusual type of ichthyosis. This inherited keratinization disorder is characterized clinically by erythema, blistering, and peeling shortly after birth. It may resolve and be replaced with thick scaling. It can lead to life-threatening complications, such as sepsis. Histologically, there is a hyperkeratosis and vacuolar degeneration. Genetically, this is an autosomal dominant disease with complete penetrance; however, 50% are spontaneous mutations. The clinical phenotype is a result of alterations in the gene(s) for keratin 1 and/or 10. We review this disorder and its therapy, which is mainly symptomatic with emollients and retinoids. [source] Homozygous familial hypercholesterolemia: Long term clinical course and plasma exchange therapy for two individual patients and review of the literatureJOURNAL OF CLINICAL APHERESIS, Issue 6 2009Roy Beigel Abstract Familial hypercholesterolemia (FH) is an autosomal dominant disease. Homozygous FH (HFH) manifests with severe hypercholesterolemia since birth (cholesterol levels >5,6 the upper normal limit), which, if untreated, leads to early onset accelerated atherosclerosis and premature coronary death, usually before the 2nd or 3rd decades of life. Various invasive procedures (iliocecal bypass, porto-caval shunt, liver transplant, and gene therapy) have been introduced for lowering low density lipoprotein (LDL) aiming at reducing atherosclerosis and improving survival of HFH patients. Of all the various methods, LDL apheresis has become the most attractive. Although its impressive effect on LDL-C reduction is well established, its long-term (of more than 10 year) effect on the atherosclerotic process and specifically cardiac end-points in HFH is hardly documented. We herewith report on the longest term lipophoresis so far reported in two HFH patients, each treated with plasma-exchange and LDL-apheresis for more than 20 years. The observations provide an opportunity to focus on various aspects regarding not only the procedure itself but also its effect on various clinical endpoints. By this description together with reviewing the literature, we discuss several issues, some of them are generalized while others are individualized, dealing with the approach of long term LDL apheresis in HFH. J. Clin. Apheresis 2009. © 2009 Wiley-Liss, Inc. [source] Phenotypic characterization of DYT13 primary torsion dystonia,MOVEMENT DISORDERS, Issue 2 2004Anna Rita Bentivoglio MD Abstract We describe the phenotype of DYT13 primary torsion dystonia (PTD) in a family first examined in 1994. A complete neurological evaluation was performed on all available family members: 8 individuals were definitely affected by dystonia. The family was re-evaluated in March 2000: at that time, 3 more individuals had developed symptoms of dystonia. Inheritance of PTD was autosomal dominant, with affected individuals spanning three consecutive generations and male-to-male transmission. Age at onset ranged from 5 to 43 years. Onset occurred either in the craniocervical region or in upper limbs. Progression was mild, and the disease course was benign in most affected individuals; generalization occurred only in 2 cases. We did not find anticipation of age at onset or of disease severity through generations. Most subjects presented with jerky, myoclonic-like dystonic movements of the neck or shoulders. DYT13-PTD is an autosomal dominant disease, with incomplete penetrance (58%). Clinical presentation and age at onset were more variable than in DYT1-PTD, and the neck was involved in most of those affected. Moreover, the individuals with generalised dystonia were not severely disabled and were able to lead independent lives. To date, this is the only family with DYT13-PTD. © 2003 Movement Disorder Society [source] Familial British dementia (FBD): a cerebral amyloidosis with systemic amyloid depositionNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2002J. L. Holton Introduction:, FBD is an autosomal dominant disease with neuropathological similarities to Alzheimer's disease (AD) as it is characterized by amyloid angiopathy, parenchymal amyloid plaque deposition and neurofibrillary degeneration. FBD is associated with a stop codon mutation in the BRI2 gene encoding a type II transmembrane protein, BriPP. Mutation results in an extended precursor protein, ABriPP, from which a C-terminal 34 amino acid peptide (ABri) is generated by furin-like proteolytic cleavage and deposited as amyloid and preamyloid in the central nervous system. Despite the morphological parallels with AD the sequences of the amyloidogenic peptides, ABri in FBD and A, in AD, are completely different. We examined systemic tissues in FBD for ABri deposition. Materials and methods:, Immunohistochemistry using an ABri-specific antibody, Ab338, counterstained with Thioflavin S and Ab338 immuno-electron microscopy identified ABri deposits and determined whether these were amyloid or preamyloid in nature. Results:, Amyloid bearing blood vessels stained positively for ABri in myocardium, uterus, bladder, spleen, pancreas, lung and skeletal muscle. ABri was also identified in either amyloid or preamyloid conformation in the parenchyma of myocardium, adrenal, pancreas and skeletal muscle. Conclusion:, This study demonstrates that FBD is the first described cerebral amyloidosis with neurofibrillary pathology and dementia to be accompanied by systemic amyloid deposition. [source] Point Mutation of an EYA1- gene Splice Site in a Patient with Oto-facio-cervical SyndromeANNALS OF HUMAN GENETICS, Issue 1 2006E. Estefanía Summary Mutations of the EYA1 gene (8q13.3) are the most common known cause of the branchio-oto-renal dysplasia (BOR), an autosomal dominant disease that includes developmental defects of branchial arch structures, middle and/or inner ear and kidney. The distinction between BOR and other dysplasias, such as oto-facio-cervical syndrome (OFC), is challenged by frequent association of the former to other diverse malformations, and by variable expressivity even within the same family. OFC is characterized by trophic alterations of the facies and shoulder girdle in addition to the malformations seen in BOR. Recent characterization of one OFC patient shed some light on the controversy over whether OFC and BOR are the same disease, and led to the hypothesis that OFC is caused by contiguous deletions of EYA1 and adjacent genes. By contrast, we show here that an OFC patient bears a single-nucleotide substitution in a splice site of EYA1. Our results indicate that not only major rearrangements, but also point mutations altering the EYA1 reading frame, can be found in patients with OFC syndrome. [source] Hereditary angioedema and pregnancyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2009Niranthari CHINNIAH Background:, Hereditary angioedema (HAE) is an autosomal dominant disease caused by a quantitative or functional defect in C1-esterase inhibitor (C1-INH). Patients with this deficiency present with episodes of angioedema which can be life-threatening. Studies examining HAE and pregnancy are scarce with little known about the interrelationship between the two. Objective:, To examine the effect, and evaluate the clinical manifestations of HAE in pregnancy using retrospective interviews of affected women. Methods:, Women with HAE who have undergone one of more pregnancies were identified throughout Australia using the national Australasian Society of Clinical Immunology and Allergy immunodeficiency database. Following informed consent, identified women were interviewed regarding their HAE status during pregnancy and the perinatal period using a questionnaire. Results:, Seven women with a total of 16 pregnancies were identified. During the first trimester of pregnancy, more than ten attacks of angioedema were experienced in six of 16 pregnancies. During the second trimester only in three of 16 pregnancies did women experience greater than ten attacks. During the post-partum period, four of seven women experienced increased frequency and severity of attacks as compared to the pre-pregnancy state. For two of four patients, this impacted on their breast-feeding routine. Conclusion:, Our study showed that women with HAE have greatly reduced or absent attacks in the last two trimesters of pregnancy, although, during the post-partum period, the majority of women experienced increased frequency and severity of attacks. [source] Facioscapulohumeral muscular dystrophy: epidemiological and molecular study in a north-east Italian population sampleCLINICAL GENETICS, Issue 6 2009ML Mostacciuolo Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease associated with a partial deletion on chromosome 4q35. Few relevant investigations have been reported on its epidemiology and were essentially based on clinical diagnosis, having been performed before recognition of the molecular mutation. We report an epidemiological survey on FSHD patients, in which the diagnosis was obtained by combined clinical and molecular evaluation. The survey concerned the north-east Italian province of Padova, an area of 871,190 inhabitants (1 January 2004). We identified 40 patients affected by FSHD based on clinical diagnosis. In 33 of them, the EcoRI fragment size in the 4q35 region ranged from 14 to 35 kb. Four other patients belonging to the same family harbored a 38-kb fragment. In these four cases, the relationship between the borderline deletion with the mild FSHD phenotype was corroborated by additional haplotype reconstruction and segregation analysis. Interestingly, the same mild facial-sparing clinical pattern was apparent only in one other patient with an EcoRI fragment of 32 kb, suggesting that this unusual FSHD phenotype may be due to very small 4q35 deletions. On the whole, estimating a prevalence rate of 44 × 10,6, our survey confirmed FSHD as one of the most frequent neuromuscular disorders in Western populations. [source] De novo germline mutation in the serine,threonine kinase STK11/LKB1 gene associated with Peutz,Jeghers syndromeCLINICAL GENETICS, Issue 1 2004I Hernan Peutz,Jeghers syndrome (PJS) is an autosomal dominant disease, characterized phenotypically by mucocutaneous pigmentation and hamartomatous polyposis. Affected patients are at an increased risk of developing gastrointestinal and other malignancies. Mutations in the STK11/LKB1 (LKB1) gene, which encodes for a serine,threonine kinase, have been identified as a genetic cause of PJS. Molecular analysis of the LKB1 gene in a simplex case of PJS revealed a substitution of cytosine (C) for guanine (G) at codon 246 in exon 6, resulting in the Tyr246X mutation. The nucleotide substitution leads to a premature stop codon at the 246 residue, predicting a truncated protein and presumed loss of kinase activity. Analysis of DNA from both parents of the PJS patient did not show this mutation, which is therefore a de novo mutation. We isolated DNA from microdissected gastrointestinal hamartomatous polyps in the PJS patient and investigated the loss of heterozygosity (LOH) at the LKB1 locus by real-time fluorescence polymerase chain reaction genotyping using a fluorescent resonance energy transfer technique. The results suggest a different mechanism from LOH in the formation of hamartomatous polyps. [source] IFN-,-producing human T cells directly induce osteoclastogenesis from human monocytes via the expression of RANKLEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2005Shigeru Kotake Abstract The current study explored our hypothesis that IFN-,-producing human T cells inhibit human osteoclast formation. Activated T cells derived from human PBMC were divided into IFN-,-producing T cells (IFN-,+ T cells) and IFN-,-non-producing T cells (IFN-,, T cells). IFN-,+ T cells were cultured with human monocytes in the presence of macrophage-CSF alone. The concentration of soluble receptor activator of NF-,B ligand (RANKL) and IFN-,, and the amount of membrane type RANKL expressed on T cells, were measured by ELISA. In the patients with early rheumatoid arthritis (RA) treated with non-steroidal anti-inflammatory drugs alone, CD4+ T cells expressing both IFN-, and RANKL were detected by flow cytometry. Surprisingly, IFN-,+ T cells, but not IFN-,, T cells, induced osteoclastogenesis from monocytes, which was completely inhibited by adding osteoprotegerin and increased by adding anti-IFN-, antibodies. The levels of both soluble and membrane type RANKL were elevated in IFN-,+ T cells. The ratio of CD4+ T cells expressing both IFN-, and RANKL in total CD4+ T cells from PBMC was elevated in RA patients. Contrary to our hypothesis, IFN-,+ human T cells induced osteoclastogenesis through the expression of RANKL, suggesting that Th1 cells play a direct role in bone resorption in Th1 dominant diseases such as RA. [source] Strategy to assess the efficiency of U1 RNA-hammerhead ribozyme constructs using GFP-tagged targetsEXPERIMENTAL DERMATOLOGY, Issue 5 2003Peter B. Cserhalmi-Friedman Abstract: The application of ribozymes for gene therapy of autosomal dominant diseases has become popularized in recent years. Further this technology has widespread utility in the treatment of any disease, acquired or inherited, by inhibition of gene expression. The design of ribozymes is usually accomplished using computer assisted design programs, however they are not very useful in predicting the behavior of the ribozyme in the in vivo setting. To overcome this technical challenge, we developed a simple in vivo strategy to accurately assess the efficiency of ribozyme cleavage that significantly enhances the computer based design programs. [source] Successful Hepatorenal Transplantation in Hereditary Amyloidosis Caused by a Frame-Shift Mutation in Fibrinogen A,-Chain GeneAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2006C. Mousson Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen A,-chain. Four mutations in the fibrinogen A,-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen A,-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be. [source] 2461: Increasing complexity of ocular genetic diseases : the case of BEST diseaseACTA OPHTHALMOLOGICA, Issue 2010M ABITBOL Purpose Monogenic diseases until recently appeared simple from a molecular genetics point of view but correlations between genotypes and phenotypes still remain difficult to establish in many diseases and for many genes. For autosomal dominant diseases such as Best Vitelliform Macular Dystrophy, supposed to be a juvenile disease, it appears that mutations of BEST1 gene can cause multiple phenotypes including early onset and late onset phenotypes as well as unexpected phenotypes such as RP. We report several novel mutations and their associated phenotypes and describe phenotypes linked to previously reoported mutations for which the phenotype had not been describe at all previously. The role of SOX9, MITF and OTX2 in the incomplete penetrance and the variable expressivity of BVMDs is duscussed as well the potential roles of SNPs occuring in coding exons Methods We used genomic PCR with appropriate primers flanking all the exons of the BEST1 gene in order to amplify them. This Genomic PCR was followed by automated sequencing and careful analysis of the sequences obtained. Results We report the case of an unusual family where the Mother II2 of the proband III1, his maternal aunt II3, his brother III3 and his first cousin IIIIV, the son of his maternal aunt, carry a missense mutatation causing apparently only electrophysiological abnormalities. The Father II1 of the proband III1 turned out to carry a stop codon instead of the fifth normal BEST1 codon. The father did not display any electrophysiological nor any clinical abnormality and has a perfect monocular and binocular vision. In contrast the proband III1 carries both mutations with a severe phenotype. Conclusion This report exemplifies the necessity to study all family members in the case of BVMDs. [source] | |||||||||||||