Analysis of IFT74 as a candidate gene for chromosome 9p-linked AL.pdf (1010.17 kB)

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

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posted on 22.11.2019, 15:23 by 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 C. 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 Hardiman, Jordan Grafman, Andrew Singleton, John Hardy, Bryan J Traynor

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.

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Published Citation

Momeni P, Schymick J, Jain S, Cookson MR, Cairns NJ, Greggio E, Greenway MJ, Berger S, Pickering-Brown S, Chiò A, Fung HC, Holtzman DM, Huey ED, Wassermann EM, Adamson J, Hutton ML, Rogaeva E, St George-Hyslop P, Rothstein JD, Hardiman O, Grafman J, Singleton A, Hardy J, Traynor BJ. Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD. BMC Neurol. 2006 Dec;6:44.

Publication Date

13/12/2006

PubMed ID

17166276

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