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<p>Abstract</p> <p>Background</p> <p>A new locus for amyotrophic lateral sclerosis – frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (<it>IFT74) </it>gene in family 476 (F476), but no mutation was detected within <it>IFT74 </it>in family 2 (F2). While neither family was sufficiently informative to definitively implicate or exclude <it>IFT74 </it>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.</p> <p>Conclusion</p> <p>Confirmation of the pathogenicity of <it>IFT74 </it>sequence variants will require screening of other chromosome 9p-linked families.</p>