Mutations in TARDBP and Their Role in Familial ALS
Author Information
Author(s): Rutherford Nicola J., Zhang Yong-Jie, Baker Matt, Gass Jennifer M., Finch NiCole A., Xu Ya-Fei, Stewart Heather, Kelley Brendan J., Kuntz Karen, Crook Richard J. P., Sreedharan Jemeen, Vance Caroline, Sorenson Eric, Lippa Carol, Bigio Eileen H., Geschwind Daniel H., Knopman David S., Mitsumoto Hiroshi, Petersen Ronald C., Cashman Neil R., Hutton Mike, Shaw Christopher E., Boylan Kevin B., Boeve Bradley, Graff-Radford Neill R., Wszolek Zbigniew K., Caselli Richard J., Dickson Dennis W., Mackenzie Ian R., Petrucelli Leonard, Rademakers Rosa
Primary Institution: Mayo Clinic
Hypothesis
Mutations in TARDBP may contribute to the development of TDP-43 proteinopathies.
Conclusion
The study identified three mutations in TARDBP that are associated with familial ALS, supporting the role of TARDBP mutations in the disease.
Supporting Evidence
- Three different heterozygous missense mutations in TARDBP were identified in 3.3% of familial ALS patients.
- No mutations were detected in sporadic ALS or other TDP-43 positive neurodegenerative diseases.
- All identified mutations affect highly conserved amino acid residues in TDP-43.
Takeaway
Some people with a type of nerve disease called ALS have changes in a gene called TARDBP, which might make their condition worse.
Methodology
The study involved mutation screening of TARDBP in a cohort of 296 patients with neurodegenerative diseases characterized by TDP-43 pathology.
Limitations
The study could not determine the segregation of mutations with disease due to the unavailability of DNA from affected relatives.
Participant Demographics
The cohort included 296 patients, with 95% being Caucasian, and a mix of familial and sporadic ALS cases.
Digital Object Identifier (DOI)
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