11 results on '"Stephan Niemann"'
Search Results
2. A common haplotype within the PON1 promoter region is associated with sporadic ALS
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Anne-Marie Wills, Ting-Jan Cho, Peter C. Sapp, John Landers, Diane McKenna-Yasek, Jonathan D. Glass, Lijia Shi, Ammar Al-Chalabi, Frank P. Diekstra, Christopher Shaw, Stephan Niemann, Meraida Polak, Ildefonso Rodriguez-Leyva, Bryan J. Traynor, P. Nigel Leigh, and Robert H. Brown
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haplotypes ,Linkage disequilibrium ,Genotype ,SNP ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Gene cluster ,medicine ,Humans ,Genetic Predisposition to Disease ,Amyotrophic lateral sclerosis ,Promoter Regions, Genetic ,Genetics ,biology ,Aryldialkylphosphatase ,case-control studies ,Amyotrophic Lateral Sclerosis ,Haplotype ,Paraoxonase ,Sequence Analysis, DNA ,General Medicine ,medicine.disease ,PON1 ,paraoxonase ,Isoenzymes ,Neurology ,Multigene Family ,biology.protein ,Original Article ,Neurology (clinical) ,Age of onset - Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder of upper and lower motor neurons. Genetic variants in the paraoxonase gene cluster have been associated with susceptibility to sporadic ALS. Because these studies have yielded conflicting results, we have further investigated this association in a larger data set. Twenty SNPs spanning the paraoxonase gene cluster were genotyped on a panel of 597 case and 692 control samples and tested for association with risk of sporadic ALS and with ALS sub-phenotypes. Our study revealed two SNPs, rs987539 and rs2074351, within the paraoxonase gene cluster that are associated with susceptibility to sporadic ALS (uncorrected p=6.47E-04 and 7.87E-04, respectively). None of the 20 SNPs displayed significant associations with age of onset, site of onset or disease survival. Using a sliding window approach, we have also identified a 5-SNP haplotype that is significantly associated with risk of sporadic ALS (p=2.75E-05). We conclude that a common haplotype within the PON1 promoter region is associated with susceptibility to sporadic ALS.
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- 2008
3. Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism
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Ulrich Müller, Dagmar Nolte, and Stephan Niemann
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Adult ,Male ,Saccharomyces cerevisiae Proteins ,Genetic Linkage ,Molecular Sequence Data ,Locus (genetics) ,Biology ,X-Linked Dystonia Parkinsonism ,Polymorphism, Single Nucleotide ,Exon ,Parkinsonian Disorders ,medicine ,Humans ,Allele ,Gene ,Dystonia ,Genetics ,Chromosomes, Human, X ,Multidisciplinary ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Parkinsonism ,Haplotype ,Membrane Transport Proteins ,DNA ,Biological Sciences ,medicine.disease ,Molecular biology ,Haplotypes ,Female - Abstract
X-linked dystonia parkinsonism (XDP) is an X-linked recessive adult onset movement disorder characterized by both dystonia and parkinsonism. We report delineation of the disease gene within a 300-kb interval of Xq13.1 by allelic association. Sequencing of this region in a patient revealed five disease-specific single-nucleotide changes (here referred to as DSC) and a 48-bp deletion unique to XDP. One of the DSCs is located within an exon of a not previously described multiple transcript system that is composed of at least 16 exons. There is a minimum of three different transcription start sites that encode four different transcripts. Two of these transcripts include distal portions of the TAF1 gene (TATA-box binding protein-associated factor 1) and are alternatively spliced. Three exons overlap with ING2 (a putative tumor suppressor) and with a homologue of CIS4 (cytokine-inducible SH2 protein 4), both of which are encoded by the opposite strand. Although all DSCs are located within this multiple transcript system, only DSC3 lies within an exon. This exon is used by all alternative transcripts making a pathogenic role of DSC3 in XDP likely. The multiple transcript system is therefore referred to as DYT3 (disease locus in XDP).
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- 2003
4. Uncoupling of Myelin Assembly and Schwann Cell Differentiation by Transgenic Overexpression of Peripheral Myelin Protein 22
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Klaus-Armin Nave, Stephan Niemann, Ueli Suter, Michael W. Sereda, and Ian R. Griffiths
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Male ,Glycosylation ,Proteolipid protein 1 ,Fluorescent Antibody Technique ,Schwann cell ,Biology ,Endoplasmic Reticulum ,Myelin assembly ,Animals, Genetically Modified ,Myelin ,Nerve Fibers ,Peripheral myelin protein 22 ,Gene expression ,medicine ,Animals ,ARTICLE ,Myelin Sheath ,Reverse Transcriptase Polymerase Chain Reaction ,General Neuroscience ,Endoplasmic reticulum ,Homozygote ,Cell Differentiation ,Molecular biology ,Rats ,Cell biology ,medicine.anatomical_structure ,Bromodeoxyuridine ,Gene Expression Regulation ,nervous system ,RNA ,Schwann Cells ,Neurology (clinical) ,Schwann cell differentiation ,Neuroscience ,Myelin Proteins - Abstract
We have generated previously transgenic rats that overexpress peripheral myelin protein 22 (PMP22) in Schwann cells. In the nerves of these animals, Schwann cells have segregated with axons to the normal 1:1 ratio but remain arrested at the promyelinating stage, apparently unable to elaborate myelin sheaths. We have examined gene expression of these dysmyelinating Schwann cells using semiquantitative reverse transcription-PCR and immunofluorescence analysis. Unexpectedly, Schwann cell differentiation appears to proceed normally at the molecular level when monitored by the expression of mRNAs encoding major structural proteins of myelin. Furthermore, an aberrant coexpression of early and late Schwann cell markers was observed. PMP22 itself acquires complex glycosylation, suggesting that trafficking of the myelin protein through the endoplasmic reticulum is not significantly impaired. We suggest that PMP22, when overexpressed, accumulates in a late Golgi–cell membrane compartment and uncouples myelin assembly from the underlying program of Schwann cell differentiation.
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- 2000
5. Familial ALS in Germany: origin of the R115G SOD1 mutation by a founder effect
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Stephan Niemann, M Gleichmann, Reinhard Dengler, S Vielhaber, Thomas F. Meyer, H Joos, Ulrich Müller, and U Reuner
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Adult ,Male ,Genotype ,animal diseases ,DNA Mutational Analysis ,SOD1 ,Short Report ,Locus (genetics) ,Biology ,Exon ,Superoxide Dismutase-1 ,Germany ,Humans ,Missense mutation ,Allele ,Genotyping ,Aged ,Genetics ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,Haplotype ,nutritional and metabolic diseases ,Exons ,Sequence Analysis, DNA ,Middle Aged ,nervous system diseases ,Psychiatry and Mental health ,Female ,Surgery ,Neurology (clinical) ,Founder effect - Abstract
Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) account for approximately 20% of patients with familial amyotrophic lateral sclerosis (FALS). In this study, sequence analysis of exons 1-5 of SOD1 in a large German cohort with FALS was performed. Among 75 affected patients, who were not obviously related probands with a positive family history, nine had missense mutations in SOD1. Four of the nine probands carry the same R115G mutation in exon 4 of the SOD1 gene. Genotyping with markers from the SOD1 locus revealed a common haplotype and shared allelic characteristics in these patients. These findings suggest that the R115G mutation in the German population originates from a common founder.
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- 2004
6. Autosomal dominant malignant and catecholamine-producing paraganglioma caused by a splice donor site mutation in SDHC
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Peter Lohse, Dieter Engelhardt, Stephan Niemann, and Ulrich Müller
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Adult ,Biology ,Carotid Body Tumor ,Exon ,Catecholamines ,Splice Donor Site ,Paraganglioma ,Genetics ,medicine ,Humans ,Transversion ,Genetics (clinical) ,Genes, Dominant ,Intron ,Membrane Proteins ,Exons ,medicine.disease ,Magnetic Resonance Imaging ,Molecular biology ,Introns ,Human genetics ,Succinate Dehydrogenase ,Mutation ,Mutation (genetic algorithm) ,Catecholamine ,Female ,RNA Splice Sites ,medicine.drug - Abstract
Mutations in SDHC cause autosomal dominant paraganglioma, type 3 (PGL3), and have to date been demonstrated in only one family. Here, we report on a novel mutation in a patient with a malignant, catecholamine-producing paraganglioma at the carotid bifurcation. The mutation is a G--T transversion at position +1 of intron 5 of the SDHC gene, leading to the deletion of exon 5 and a shift in the reading frame.
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- 2003
7. An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis
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Elly M C A de Bruyn, Rogier A. Oldenburg, Jean-Pierre Bayley, Anne-Paule Gimenez-Roqueplo, Anne van Linge, Ronald R. de Krijger, Paul Komminoth, Judith Favier, Esther Korpershoek, Aurel Perren, Despoina Alataki, Bart-Jeroen Petri, Laurence Amar, Francesco Ferraù, Eric Van Marck, Jacques W.M. Lenders, Hein F.B.M. Sleddens, José Gaal, Hilde Dannenberg, Pieter Derkx, Massimo Mannelli, Julie Rivière, Stephan Niemann, Jérôme Bertherat, Winand N.M. Dinjens, Mark-Paul F M Vrancken Peeters, Wouter W. de Herder, Cécile Badoual, Albert A.J. Verhofstad, Frédérique Tissier, Francien H van Nederveen, Jerney François, Karel Pacak, Patrick J. Pollard, Adriaan P. de Bruïne, Tchao Meatchi, Wim C. J. Hop, Eamonn R. Maher, Pathology, Clinical Genetics, Surgery, Epidemiology, Internal Medicine, Otorhinolaryngology and Head and Neck Surgery, and University of Groningen
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Male ,Pathology ,endocrine system diseases ,SDHB ,FEATURES ,DNA Mutational Analysis ,SDHA ,Adrenal Gland Neoplasms ,HYPOXIA ,MITOCHONDRIAL RESPIRATORY-CHAIN ,Gene mutation ,DISEASE ,Paraganglioma ,MALIGNANT PHEOCHROMOCYTOMAS ,Medicine ,Child ,Cardiovascular diseases [NCEBP 14] ,Syndrome ,Middle Aged ,Immunohistochemistry ,Succinate Dehydrogenase ,Mitochondrial respiratory chain ,Oncology ,Female ,Carney Stratakis syndrome ,Adult ,medicine.medical_specialty ,endocrine system ,Adolescent ,Blotting, Western ,Pheochromocytoma ,Article ,Young Adult ,Germline mutation ,SDG 3 - Good Health and Well-being ,ENZYMATIC-ACTIVITY ,Humans ,Germ-Line Mutation ,Aged ,COMPLEX-II ,SUCCINATE ,business.industry ,Membrane Proteins ,LINE MUTATIONS ,medicine.disease ,UPDATE ,Human medicine ,SDHD ,business - Abstract
Contains fulltext : 80017.pdf (Publisher’s version ) (Closed access) BACKGROUND: Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. METHODS: Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. FINDINGS: SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. INTERPRETATION: Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. FUNDING: The Netherlands Organisation for Scientific Research, Dutch Cancer Society, Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Sante et de la Recherche Medicale, and a PHRC grant COMETE 3 for the COMETE network.
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- 2009
8. DNA methylation markers predict outcome in node-positive, estrogen receptor-positive breast cancer with adjuvant anthracycline-based chemotherapy
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Achim Plum, Dimo Dietrich, Ralf Lesche, Frédérique Spyratos, Manfred Schmitt, Stephan Niemann, Oliver Hartmann, Katrin Welzel, Anne Fassbender, John W.M. Martens, Vincent Vuaroqueaux, Serenella Eppenberger-Castori, John A. Foekens, Sabine Maier, Nadia Harbeck, Florence Lerebours, and Medical Oncology
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Oncology ,Cancer Research ,medicine.medical_specialty ,Candidate gene ,Neoplasms, Hormone-Dependent ,Anthracycline ,Population ,Breast Neoplasms ,Biology ,Breast cancer ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,Anthracyclines ,education ,Homeodomain Proteins ,education.field_of_study ,Proportional hazards model ,Methylation ,DNA Methylation ,Genes, erbB-2 ,medicine.disease ,Prognosis ,Treatment Outcome ,Receptors, Estrogen ,Chemotherapy, Adjuvant ,Lymphatic Metastasis ,DNA methylation ,Cancer research ,Biomarker (medicine) ,Female ,Biomarkers ,Transcription Factors - Abstract
Purpose: We have shown that DNA methylation of the PITX2 gene predicts risk of distant recurrence in steroid hormone receptor-positive, node-negative breast cancer. Here, we present results from a multicenter study investigating whether PITX2 and other candidate DNA methylation markers predict outcome in node-positive, estrogen receptor-positive, HER-2-negative breast cancer patients who received adjuvant anthracycline-based chemotherapy. Experimental Design: Using a microarray platform, we analyzed DNA methylation in regulatory regions of PITX2 and 60 additional candidate genes in 241 breast cancer specimens. Using Cox regression analysis, we assessed the predictive power of the individual marker/marker panel candidates. Clinical endpoints were time to distant metastasis, disease-free survival, and overall survival. A nested bootstrap/cross-validation strategy was applied to identify and validate marker panels. Results: DNA methylation of PITX2 and 14 other genes was correlated with clinical outcome. In multivariate models, each methylation marker added significant information to established clinical factors. A four-marker panel including PITX2, BMP4, FGF4, and C20orf55 was identified that resulted in improvement of outcome prediction compared with PITX2 alone. Conclusions: This study provides further evidence for the PITX2 biomarker, which has now been successfully confirmed to predict outcome among different breast cancer patient populations. We further identify new DNA methylation biomarkers, three of which can be combined into a panel with PITX2 to increase the outcome prediction performance in our anthracycline-treated primary breast cancer population. Our results show that a well-defined panel of DNA methylation markers enables outcome prediction in lymph node-positive, HER-2-negative breast cancer patients treated with anthracycline-based chemotherapy.
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- 2009
9. Phenotypic and Molecular Analyses of X-linked Dystonia-Parkinsonism ('Lubag') in Women
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Ulrich Müller, Dagmar Nolte, Mezzanie C. Mayo, Filipinas F. Natividad, Joel Advincula, Stephan Niemann, and Virgilio Gerald H. Evidente
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Neurological disorder ,X-Linked Dystonia Parkinsonism ,Parkinsonian Disorders ,Arts and Humanities (miscellaneous) ,medicine ,Humans ,Aged ,Dystonia ,Parkinsonism ,Genetic Diseases, X-Linked ,Chorea ,Middle Aged ,Focal dystonia ,medicine.disease ,nervous system diseases ,Surgery ,Phenotype ,Haplotypes ,Case-Control Studies ,Female ,Neurology (clinical) ,medicine.symptom ,Age of onset ,Psychology ,Myoclonus - Abstract
Background X-linked dystonia-parkinsonism (XDP) or “lubag” is an X-linked recessive disorder that afflicts Filipino men, and rarely, women. Genetic confirmation is performed through haplotyping or detection of disease-specific changes in the DYT3 gene. Objective To describe the phenotypes and molecular data of 8 symptomatic female patients with XDP from 5 kindreds. Methods Case series. Results The average age of onset of symptoms was 52 years (range, 26-75 years). Six of 8 patients had parkinsonism, whereas only 1 had dystonia. The initial symptom was focal tremor or parkinsonism in 4, chorea in 3, and focal dystonia (cervical) in 1. Seven of 8 patients had slow or no progression of their symptoms and required no treatment. The patient with disabling parkinsonism was responsive to carbidopa/levodopa. Seven were heterozygous for the XDP haplotype, whereas 1 was homozygous. Conclusions The phenotypes of female patients with XDP may include parkinsonism, dystonia, myoclonus, tremor, and chorea. The dystonia, if present, is mild and usually nonprogressive. Similar to men with XDP, parkinsonism is a frequent symptom in women. In contrast to men, affected women have a more benign phenotype, older age of onset, and milder course. Extreme X-inactivation mosaic may be a cause of symptoms in women with XDP, but a homozygously affected woman has also been observed.
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- 2004
10. Homozygous WNT3 Mutation Causes Tetra-Amelia in a Large Consanguineous Family
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Ute Aulepp, Ulrich Stahl, James L. Weber, Ulrich Müller, Filon Pascu, Lee Niswander, Stephan Niemann, and Chengfeng Zhao
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Male ,Ectromelia ,Nonsense mutation ,Locus (genetics) ,Consanguinity ,Biology ,Wnt3 Protein ,symbols.namesake ,Mice ,Report ,Genetics ,medicine ,Animals ,Humans ,Genetics(clinical) ,Genetics (clinical) ,Haplotype ,Genetic disorder ,Chromosome Mapping ,Proteins ,Sequence Analysis, DNA ,medicine.disease ,Disease gene identification ,Null allele ,Pedigree ,Fibroblast Growth Factors ,Wnt Proteins ,Haplotypes ,Mutation ,Mendelian inheritance ,symbols ,Female ,Fibroblast Growth Factor 10 ,Chromosomes, Human, Pair 17 - Abstract
Tetra-amelia is a rare human genetic disorder characterized by complete absence of all four limbs and other anomalies. We studied a consanguineous family with four affected fetuses displaying autosomal recessive tetra-amelia and craniofacial and urogenital defects. By homozygosity mapping, the disease locus was assigned to chromosome 17q21, with a maximum multipoint LOD score of 2.9 at markers D17S931, D17S1785, D17SS1827, and D17S1868. Further fine mapping defined a critical interval of approximately 8.9 Mb between D17S1299 and D17S797. We identified a homozygous nonsense mutation (Q83X) in the WNT3 gene in affected fetuses of the family. WNT3, a human homologue of the Drosophila wingless gene, encodes a member of the WNT family known to play key roles in embryonic development. The Q83X mutation truncates WNT3 at its amino terminus, suggesting that loss of function is the most likely cause of the disorder. Our findings contrast with the observation of early lethality in mice homozygous for null alleles of Wnt3. To our knowledge, this is the first report of a mutation in a WNT gene associated with a Mendelian disorder. The identification of a WNT3 mutation in tetra-amelia indicates that WNT3 is required at the earliest stages of human limb formation and for craniofacial and urogenital development.
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- 2004
11. Refined linkage disequilibrium and physical mapping of the gene locus for X-linked dystonia-parkinsonism (DYT3)
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Usha Peters, Elena G. Bochukova, Ulrich Müller, Andrea H. Németh, Eimear Dunne, Julie Brown, Elaine R. Levy, Roger D. Cox, Dagmar Nolte, Anthony P. Monaco, Markus Kostrzewa, Stephan Niemann, Hans-Hilger Ropers, Eileen Fraser, and Robin Butler
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Genetic Markers ,Linkage disequilibrium ,X Chromosome ,Genetic Linkage ,X-Linked Dystonia Parkinsonism ,Biology ,Linkage Disequilibrium ,Contig Mapping ,Gene mapping ,Parkinsonian Disorders ,Genetics ,Humans ,Gene ,X chromosome ,Expressed Sequence Tags ,Contig ,Haplotype ,food and beverages ,Chromosome Mapping ,Syndrome ,Cosmids ,Physical Chromosome Mapping ,Dystonia ,Tandem Repeat Sequences ,Cosmid - Abstract
X-linked dystonia-parkinsonism (XDP) is a recessive disorder characterized by generalized dystonia with some patients exhibiting parkinsonism. The disease gene, DYT3, is located between DXS453 (DXS993) and DXS559, and strongest linkage disequilibrium is found distal to DXS7117 and proximal to DXS559. We have isolated and analyzed four novel polymorphic markers between DXS7117 and DXS559 and, by haplotype analysis, have narrowed the candidate interval to
- Published
- 1999
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