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Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset.

Publication ,  Journal Article
Theunissen, F; Anderton, RS; Mastaglia, FL; James, I; Bedlack, R; Akkari, PA
Published in: Sci Rep
August 30, 2022

Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleotide (TTTA) repeat variant in NEFH was selected using an in-silico short structural variant (SSV) evaluation algorithm and investigated in two cohorts of North American sALS patients, both separately and combined (Duke cohort n = 138, Coriell cohort n = 333; combined cohort n = 471), compared to a group of healthy controls from the Coriell Institute biobank (n = 496). Stratification according to site of disease onset revealed that the 9 TTTA allele was associated with reduced disease risk, specifically confined to spinal-onset sALS patients in the Duke cohort (p = 0.001). Furthermore, carriage of the 10 TTTA allele was associated with a 2.7 year later age of disease onset in the larger combined sALS cohort (p = 0.02). These results suggest that the 9 and 10 TTTA motif length may have a protective advantage for potentially lowering the risk of sALS and delaying the age of disease onset, however, these results need to be replicated in larger multicenter and multi-ethnic cohorts.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

August 30, 2022

Volume

12

Issue

1

Start / End Page

14739

Location

England

Related Subject Headings

  • Polymorphism, Genetic
  • Neurofilament Proteins
  • Mutation
  • Intermediate Filaments
  • Humans
  • Genetic Predisposition to Disease
  • Amyotrophic Lateral Sclerosis
 

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Theunissen, F., Anderton, R. S., Mastaglia, F. L., James, I., Bedlack, R., & Akkari, P. A. (2022). Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset. Sci Rep, 12(1), 14739. https://doi.org/10.1038/s41598-022-18942-x
Theunissen, Frances, Ryan S. Anderton, Frank L. Mastaglia, Ian James, Richard Bedlack, and P Anthony Akkari. “Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset.Sci Rep 12, no. 1 (August 30, 2022): 14739. https://doi.org/10.1038/s41598-022-18942-x.
Theunissen F, Anderton RS, Mastaglia FL, James I, Bedlack R, Akkari PA. Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset. Sci Rep. 2022 Aug 30;12(1):14739.
Theunissen, Frances, et al. “Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset.Sci Rep, vol. 12, no. 1, Aug. 2022, p. 14739. Pubmed, doi:10.1038/s41598-022-18942-x.
Theunissen F, Anderton RS, Mastaglia FL, James I, Bedlack R, Akkari PA. Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset. Sci Rep. 2022 Aug 30;12(1):14739.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

August 30, 2022

Volume

12

Issue

1

Start / End Page

14739

Location

England

Related Subject Headings

  • Polymorphism, Genetic
  • Neurofilament Proteins
  • Mutation
  • Intermediate Filaments
  • Humans
  • Genetic Predisposition to Disease
  • Amyotrophic Lateral Sclerosis