Analysis of IFT74 As a Candidate Gene for Chromosome 9p-linked ALS-FTD

Overview

Journal BMC Neurol

Publisher Biomed Central

Specialty Neurology

Date 2006 Dec 15

PMID 17166276

Citations 35

Authors

Parastoo Momeni

Jennifer Schymick

Shushant Jain

Mark R Cookson

Nigel J Cairns

Elisa Greggio

Matthew J Greenway

Stephen Berger

Stuart Pickering-Brown

Adriano Chio

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 Hardiman

Jordan Grafman

Andrew Singleton

John Hardy

Bryan J Traynor

Affiliations

Soon will be listed here.

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.

Citing Articles

Mendelian and Sporadic FTD: Disease Risk and Avenues from Genetics to Disease Pathways Through In Silico Modelling.

Manzoni C, Ferrari R Adv Exp Med Biol. 2021; 1281:283-296.

PMID: 33433881 DOI: 10.1007/978-3-030-51140-1_17.

The Genetics of Expansions.

Gijselinck I, Cruts M, Van Broeckhoven C Cold Spring Harb Perspect Med. 2017; 8(4).

PMID: 28130313 PMC: 5880162. DOI: 10.1101/cshperspect.a026757.

Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

Hosseinzadeh M, Nikseresht S, Khodagholi F, Naderi N, Maghsoudi N J Mol Neurosci. 2016; 58(4):432-40.

PMID: 26738731 DOI: 10.1007/s12031-015-0703-6.

Phenotypic Heterogeneity of Monogenic Frontotemporal Dementia.

Benussi A, Padovani A, Borroni B Front Aging Neurosci. 2015; 7:171.

PMID: 26388768 PMC: 4555036. DOI: 10.3389/fnagi.2015.00171.

Frontotemporal dementia: a bridge between dementia and neuromuscular disease.

Ng A, Rademakers R, Miller B Ann N Y Acad Sci. 2015; 1338:71-93.

PMID: 25557955 PMC: 4399703. DOI: 10.1111/nyas.12638.

References

Goldstein L, Philp A . The road less traveled: emerging principles of kinesin motor utilization. Annu Rev Cell Dev Biol. 1999; 15:141-83. DOI: 10.1146/annurev.cellbio.15.1.141. View

Momeni P, Rogaeva E, Van Deerlin V, Yuan W, Grafman J, Tierney M . Genetic variability in CHMP2B and frontotemporal dementia. Neurodegener Dis. 2006; 3(3):129-33. DOI: 10.1159/000094771. View

Brooks B, Miller R, Swash M, Munsat T . El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2001; 1(5):293-9. DOI: 10.1080/146608200300079536. View

Wilson C, Grace G, Munoz D, He B, Strong M . Cognitive impairment in sporadic ALS: a pathologic continuum underlying a multisystem disorder. Neurology. 2001; 57(4):651-7. DOI: 10.1212/wnl.57.4.651. View

Yang Y, Hentati A, Deng H, Dabbagh O, Sasaki T, Hirano M . The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet. 2001; 29(2):160-5. DOI: 10.1038/ng1001-160. View

Mase G, Ros S, Gemma A, Bonfigli L, Carraro N, Cazzato G . ALS with variable phenotypes in a six-generation family caused by leu144phe mutation in the SOD1 gene. J Neurol Sci. 2001; 191(1-2):11-8. DOI: 10.1016/s0022-510x(01)00625-6. View

Snowden J, Neary D, Mann D . Frontotemporal dementia. Br J Psychiatry. 2002; 180:140-3. DOI: 10.1192/bjp.180.2.140. View

Cann H, De Toma C, Cazes L, Morel V, Piouffre L, Bodmer J . A human genome diversity cell line panel. Science. 2002; 296(5566):261-2. DOI: 10.1126/science.296.5566.261b. View

Lomen-Hoerth C, Anderson T, Miller B . The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology. 2002; 59(7):1077-9. DOI: 10.1212/wnl.59.7.1077. View

10.

Lomen-Hoerth C, Murphy J, Langmore S, Kramer J, Olney R, Miller B . Are amyotrophic lateral sclerosis patients cognitively normal?. Neurology. 2003; 60(7):1094-7. DOI: 10.1212/01.wnl.0000055861.95202.8d. View

11.

Rosso S, Donker Kaat L, Baks T, Joosse M, de Koning I, Pijnenburg Y . Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain. 2003; 126(Pt 9):2016-22. DOI: 10.1093/brain/awg204. View

12.

Chen Y, Bennett C, Huynh H, Blair I, Puls I, Irobi J . DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am J Hum Genet. 2004; 74(6):1128-35. PMC: 1182077. DOI: 10.1086/421054. View

13.

Johnson J, Ostojic J, Lannfelt L, Glaser A, Basun H, Rogaeva E . No evidence for tau duplications in frontal temporal dementia families showing genetic linkage to the tau locus in which tau mutations have not been found. Neurosci Lett. 2004; 363(2):99-101. DOI: 10.1016/j.neulet.2004.03.070. View

14.

Munch C, Sedlmeier R, Meyer T, Homberg V, Sperfeld A, Kurt A . Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology. 2004; 63(4):724-6. DOI: 10.1212/01.wnl.0000134608.83927.b1. View

15.

Nishimura A, Mitne-Neto M, Silva H, Richieri-Costa A, Middleton S, Cascio D . A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet. 2004; 75(5):822-31. PMC: 1182111. DOI: 10.1086/425287. View

16.

Hudson A . Amyotrophic lateral sclerosis and its association with dementia, parkinsonism and other neurological disorders: a review. Brain. 1981; 104(2):217-47. DOI: 10.1093/brain/104.2.217. View

17.

Rosen D, Siddique T, Patterson D, Figlewicz D, Sapp P, Hentati A . Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993; 362(6415):59-62. DOI: 10.1038/362059a0. View

18.

Ince P, Lowe J, Shaw P . Amyotrophic lateral sclerosis: current issues in classification, pathogenesis and molecular pathology. Neuropathol Appl Neurobiol. 1998; 24(2):104-17. DOI: 10.1046/j.1365-2990.1998.00108.x. View

19.

Hutton M, Lendon C, Rizzu P, Baker M, Froelich S, Houlden H . Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998; 393(6686):702-5. DOI: 10.1038/31508. View

20.

Chow T, Miller B, Hayashi V, Geschwind D . Inheritance of frontotemporal dementia. Arch Neurol. 1999; 56(7):817-22. PMC: 5786271. DOI: 10.1001/archneur.56.7.817. View