Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD

Parastoo Momeni, Jennifer Schymick, Shushant Jain, Mark R Cookson, Nigel J Cairns, Elisa Greggio, Matthew J Greenway, Stephen Berger, Stuart Pickering-Brown, Adriano Chiò, Hon Chung Fung, David M Holtzman, Edward D Huey, Eric M Wassermann, Jennifer Adamson, Michael L Hutton, Ekaterina Rogaeva, Peter St George-Hyslop, Jeffrey D Rothstein, Orla HardimanJordan Grafman, Andrew Singleton, John Hardy, Bryan J Traynor

    Research output: Contribution to journalArticlepeer-review


    BACKGROUND: A new locus for amyotrophic lateral sclerosis--frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p.

    METHODS: We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus.

    RESULTS: Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 (F476), but no mutation was detected within IFT74 in family 2 (F2). While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids) led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420). An additional sequence variant (G58D) was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples.

    CONCLUSION: Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families.

    Original languageEnglish
    Article number44
    JournalBMC Neurology
    Publication statusPublished - 13 Dec 2006


    • Amyotrophic Lateral Sclerosis
    • Base Sequence
    • Chromosome Aberrations
    • Chromosome Mapping
    • Chromosomes, Human, Pair 9
    • Dementia
    • Genetic Predisposition to Disease
    • Heterozygote
    • Humans
    • Male
    • Middle Aged
    • Molecular Sequence Data
    • Mutation
    • North America
    • Polymorphism, Single Nucleotide
    • Prevalence
    • Risk Assessment
    • Risk Factors
    • Journal Article
    • Research Support, N.I.H., Extramural
    • Research Support, N.I.H., Intramural
    • Research Support, Non-U.S. Gov't

    Research Beacons, Institutes and Platforms

    • Dementia@Manchester


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