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Keywords {🔍}

iii, disease, article, chromosome, pubmed, google, scholar, linkage, clinical, haplotype, figure, frontotemporal, family, tdp, cas, region, dementia, degeneration, recombination, ftldmnd, lod, ftld, genes, pedigree, locus, analysis, mnd, lobar, reported, affected, research, genetic, individuals, lateral, sclerosis, years, markers, candidate, inclusions, data, motor, amyotrophic, gene, positive, peter, members, score, cases, families, australia,

Topics {✒️}

ubiquitin-positive tau-negative inclusions motor neurone disease steele-richardson-olszewski syndrome high-resolution fine mapping full size image article download pdf pre-publication history multi-generational australian family open access article high-resolution recombination map avoid exon/intron boundaries ubiquitin-immunoreactive inclusions characteristic chromosome 9p-linked als-ftd ubiquitin-positive achromatic neurons multi-point lod score chromosome 9p-linked ftld-mnd motor neuron disease flanking intronic sequence large ftld-mnd kindreds chromosomal region 9p21-9q12 genome-wide linkage analysis neuronal cytoplasmic inclusions dna sequence analysis amyotrophic lateral sclerosis flanking intronic regions frontotemporal lobar degeneration medical research council large ftld-mnd family privacy choices/manage cookies normal australian population affection status revealed chromosome 9p-linked families anterior temporal lobes nuclear protein implicated exact recombination breakpoint centromeric recombination breakpoint genome-wide scan flanking intronic sequences late-onset ad patients lower motor neurons published recombination boundaries tdp-43 immunopositive skein tdp-43 positive pathology existing hippocampal sclerosis autosomal dominant inheritance tau-positive pathology pericak-vance ma authors’ original file parasagittal motor cortex positive lod scores

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         headline:Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9
         description:Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease haplotype, highlights the possibility that late-onset AD patients in the other linked pedigrees may be mis-classified as sporadic dementia cases.
         datePublished:2008-08-29T00:00:00Z
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            Dementia With Lewy Body
            Cresyl Violet
            Motor Neurone Disease
            Recombination Breakpoint
            Flank Intronic Sequence
            Neurology
            Neurochemistry
            Neurosurgery
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      headline:Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9
      description:Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease haplotype, highlights the possibility that late-onset AD patients in the other linked pedigrees may be mis-classified as sporadic dementia cases.
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      keywords:
         Dementia With Lewy Body
         Cresyl Violet
         Motor Neurone Disease
         Recombination Breakpoint
         Flank Intronic Sequence
         Neurology
         Neurochemistry
         Neurosurgery
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            name:Garvan Institute of Medical Research
            address:
               name:Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Elizabeth M Thompson
      affiliation:
            name:Women's and Children's Hospital
            address:
               name:SA Clinical Genetics Service, Women's and Children's Hospital, Adelaide, Australia
               type:PostalAddress
            type:Organization
      name:Peter Blumbergs
      affiliation:
            name:Institute of Medical and Veterinary Science
            address:
               name:Institute of Medical and Veterinary Science, Adelaide, Australia
               type:PostalAddress
            type:Organization
      name:William S Brooks
      affiliation:
            name:Prince of Wales Medical Research Institute
            address:
               name:Prince of Wales Medical Research Institute, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:University of New South Wales
            address:
               name:University of New South Wales, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Clement T Loy
      affiliation:
            name:Prince of Wales Medical Research Institute
            address:
               name:Prince of Wales Medical Research Institute, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:University of New South Wales
            address:
               name:University of New South Wales, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:Garvan Institute of Medical Research
            address:
               name:Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Carol Dobson-Stone
      affiliation:
            name:Prince of Wales Medical Research Institute
            address:
               name:Prince of Wales Medical Research Institute, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:University of New South Wales
            address:
               name:University of New South Wales, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Peter K Panegyres
      affiliation:
            name:Department of Health
            address:
               name:Neurosciences Unit, Department of Health, Perth, Australia
               type:PostalAddress
            type:Organization
            name:Neurodegenerative Disorders Research
            address:
               name:Neurodegenerative Disorders Research, Subiaco, Australia
               type:PostalAddress
            type:Organization
      name:Jane Hecker
      affiliation:
            name:College Grove Private Hospital
            address:
               name:College Grove Private Hospital, Adelaide, Australia
               type:PostalAddress
            type:Organization
      name:Garth A Nicholson
      affiliation:
            name:Concord Hospital
            address:
               name:Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord Hospital, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:University of Sydney
            address:
               name:Faculty of Medicine, University of Sydney, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Glenda M Halliday
      affiliation:
            name:Prince of Wales Medical Research Institute
            address:
               name:Prince of Wales Medical Research Institute, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:University of New South Wales
            address:
               name:University of New South Wales, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Peter R Schofield
      affiliation:
            name:Prince of Wales Medical Research Institute
            address:
               name:Prince of Wales Medical Research Institute, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:University of New South Wales
            address:
               name:University of New South Wales, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:Garvan Institute of Medical Research
            address:
               name:Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Prince of Wales Medical Research Institute, Sydney, Australia
      name:University of New South Wales, Sydney, Australia
      name:Garvan Institute of Medical Research, Sydney, Australia
      name:Prince of Wales Medical Research Institute, Sydney, Australia
      name:University of New South Wales, Sydney, Australia
      name:Garvan Institute of Medical Research, Sydney, Australia
      name:SA Clinical Genetics Service, Women's and Children's Hospital, Adelaide, Australia
      name:Institute of Medical and Veterinary Science, Adelaide, Australia
      name:Prince of Wales Medical Research Institute, Sydney, Australia
      name:University of New South Wales, Sydney, Australia
      name:Prince of Wales Medical Research Institute, Sydney, Australia
      name:University of New South Wales, Sydney, Australia
      name:Garvan Institute of Medical Research, Sydney, Australia
      name:Prince of Wales Medical Research Institute, Sydney, Australia
      name:University of New South Wales, Sydney, Australia
      name:Neurosciences Unit, Department of Health, Perth, Australia
      name:Neurodegenerative Disorders Research, Subiaco, Australia
      name:College Grove Private Hospital, Adelaide, Australia
      name:Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord Hospital, Sydney, Australia
      name:Faculty of Medicine, University of Sydney, Sydney, Australia
      name:Prince of Wales Medical Research Institute, Sydney, Australia
      name:University of New South Wales, Sydney, Australia
      name:Prince of Wales Medical Research Institute, Sydney, Australia
      name:University of New South Wales, Sydney, Australia
      name:Garvan Institute of Medical Research, Sydney, Australia

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