Research Notes

Genetic factors and their action in persistent stuttering

Carlos Frigerio Domingues, Tae-Un Han, and Dennis Drayna

National Institutes of Health, Bethesda, Maryland

Published:
March 7, 2019
September 18, 2024

The identification of stuttering-associated mutations in humans has allowed the engineering of these mutations into mice to develop an animal model of stuttering. Although mice lack the speech articulatory apparatus analogous to that of humans, they share a number of brain functional regions associated with speech in humans. It has thus been hypothesized that the mouse could provide a useful model for the volitional control of vocalization, which evidence suggests is a problem in human stuttering. Mice carrying mutations equivalent to those causing human stuttering have been successfully generated, and while many aspects of their vocalizations are normal, it was discovered that the mutant mice have abnormally increased pauses during their vocalization (Barnes et al. Current Biology 2016).  These pauses were shown to be similar to the features of stuttering speech in humans who carried these mutations (Barnes et al, Current Biology, 2016.

Studies of these “stuttering” mice did not reveal any changes in their tissues, and they behave normally in a wide variety of mouse behavior tests. This suggests that any changes in the brain caused by the human stuttering mutations would be subtle or highly localized.  The latest studies are now pinpointing the cells specifically affected by the mutation, and their location in the brains of these mice.

References

Opinions expressed in this article are those of the author(s) and not of the International Fluency Association.References:

  1. Kang C, Riazuddin S, Mundorff J, Krasnewich D, Friedman P, Mullikin J, and Drayna D. Lysosomal Enzyme Targetting Pathway Mutaions and Persistent Stuttering. New England Journal of Medicine362:677-685 (2010) https://www.nejm.org/doi/10.1056/NEJMoa0902630?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dwww.ncbi.nlm.nih.gov
  2. Fisher S. Genetic Susceptibility to Stuttering. Editorial, New England Journal of Medicine 362:75—752 (2010) https://www.ncbi.nlm.nih.gov/pubmed/20147708
  3. Raza MH, Mattera M, Morell R, Sainz E, Rahn R, Gutierrez J, Paris E, Root J, Solomon B, Brewer C, Basra M, Khan S, Riazuddin S, Braun A, Bonifacino J, and Drayna D. Association of rare variants in AP4E1, a component of intracellular trafficking, with persistent stuttering. American Journal of Human Genetics97:715-725 (2015).https://www.sciencedirect.com/science/article/pii/S0002929715004097?via%3Dihub
  4. Barnes T, Wozniak D, Gutierrez J, Han T-U, Drayna D, and Holy T. A mutation associated with stuttering alters mouse pup ultrasonic vocalizations. Current Biology26:1-10 (2016) https://www.sciencedirect.com/science/article/pii/S0960982216301798?via%3Dihub
  5. Frigerio-Domingues C, Drayna D. Genetic contributions to stuttering: the current evidence.  Mol Genet Genomic Med. 2017 Feb 19;5(2):95-102. doi: 10.1002/mgg3.276.  eCollection 2017 Mar. https://www.ncbi.nlm.nih.gov/pubmed/28361094

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