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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

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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