Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2018 Sep 25;91(13):e1215-e1219.
doi: 10.1212/WNL.0000000000006245. Epub 2018 Aug 22.

The relationship between deficit in digit span and genotype in nonsense mutation Duchenne muscular dystrophy

Mathula Thangarajh  1 , Gary L Elfring  2 , Panayiota Trifillis  2 , Joseph McIntosh  2 , Stuart W Peltz  2 ; Ataluren Phase 2b Study Group
Collaborators, Affiliations
Clinical Trial

The relationship between deficit in digit span and genotype in nonsense mutation Duchenne muscular dystrophy

Mathula Thangarajh et al. Neurology. .

Abstract

Objective: To evaluate the relationship between deficit in digit span and genotype in nonsense mutation (nm) Duchenne muscular dystrophy (DMD) (nmDMD).

Methods: We investigated the relationship between normalized digit-span forward (d-sf) and digit-span backward (d-sb) scores to the location of nmDMD mutations in 169 participants ≥5 to ≤20 years who participated in a phase 2b clinical trial. Because alternative promoters are found upstream of DMD exons 30, 45, and 63, we correlated d-sf and d-sb to the specific nmDMD mutation location.

Results: Participants with nm downstream of exon 30, downstream of exon 45, and downstream of exon 63 had significantly lower normalized d-sf scores (p < 0.0001). Participants with nm downstream of exon 45 in addition had significantly lower normalized d-sb score (p < 0.04). There was no significant difference in the normalized d-sb score in participants with mutations upstream or downstream of DMD exon 30 or upstream or downstream of DMD exon 63.

Conclusion: Our data provide evidence that specific cognitive deficits correlate to genotype in individuals with nmDMD, highlighting the critical role of brain-specific dystrophin isoforms in the neurobiological manifestations of this disease.

Clinicaltrialsgov identifier: NCT02090959.

PubMed Disclaimer

Figures

Figure
Figure. Normalized digit-span forward (d-sf) score, normalized digit-span backward (d-sb) score, and Duchenne muscular dystrophy (DMD) mutation location
(A) Normalized d-sf score. (B) Normalized d-sb score.
See this image and copyright information in PMC

References

    1. Pichavant C, Aartsma-Rus A, Clemens PR, et al. Current status of pharmaceutical and genetic therapeutic approaches to treat DMD. Mol Ther 2011;19:830–840. - PMC - PubMed
    1. Hendriksen JG, Vles JS. Neuropsychiatric disorders in males with Duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive–compulsive disorder. J Child Neurol 2008;23:477–481. - PubMed
    1. Bushby KM, Appleton R, Anderson LV, Welch JL, Kelly P, Gardner-Medwin D. Deletion status and intellectual impairment in Duchenne muscular dystrophy. Dev Med Child Neurol 1995;37:260–269. - PubMed
    1. Felisari G, Martinelli Boneschi F, Bardoni A, et al. Loss of Dp140 dystrophin isoform and intellectual impairment in Duchenne dystrophy. Neurology 2000;55:559–564. - PubMed
    1. Moizard MP, Toutain A, Fournier D, et al. Severe cognitive impairment in DMD: obvious clinical indication for Dp71 isoform point mutation screening. Eur J Hum Genet 2000. ;8:552–556. - PubMed

Publication types

Substances

Associated data