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 journalArticle

Abstract

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 (US)
Article number44
JournalBMC neurology
Volume6
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Clinical Neurology

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    Momeni, P., Schymick, J., Jain, S., Cookson, M. R., Cairns, N. J., Greggio, E., Greenway, M. J., Berger, S., Pickering-Brown, S., Chiò, A., Fung, H. C., Holtzman, D. M., Huey, E. D., Wassermann, E. M., Adamson, J., Hutton, M. L., Rogaeva, E., St. George-Hyslop, P., Rothstein, J. D., ... Traynor, B. J. (2006). Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD. BMC neurology, 6, [44]. https://doi.org/10.1186/1471-2377-6-44