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Amyotroph Lateral Scler Frontotemporal Degener. 2017 May;18(3-4):175-181. doi: 10.1080/21678421.2016.1257024. Epub 2016 Dec 23.

Proposed association between the hexanucleotide repeat of C9orf72 and opposability index of the thumb.

Author information

1
a Department of Basic and Clinical Neurosciences , Maurice Wohl Clinical Neuroscience Institute, King's College London , London , UK and.
2
b Department of Stem Cell and Regenerative Biology , Center for Brain Science and Harvard Stem Cell Institute, Harvard University , Cambridge , MA , USA.

Abstract

OBJECTIVE:

Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by motor neuron and sub-cerebral projection neuron degeneration. We sought to explore the particular susceptibility of humans to neurodegeneration and whether any characteristic human features might predispose to selective vulnerability of the critical motor circuitry in ALS. The pathophysiology of the C9orf72 repeat is not yet understood, despite its role as a common cause of ALS and frontotemporal dementia.

METHODS:

We examined the development of the monosynaptic cortico-motoneuronal system, key to skilled hand movements, measured by the thumb opposability index, and its relationship to the C9orf72 hexanucleotide repeat expansion, a strong predisposing factor for neurodegeneration, using the genomic tool BLAST.

RESULTS:

We found a statistically significant linear relationship between the C9orf72 hexanucleotide bit score, a measure of genomic conservation of the aligned region across different species, and the thumb opposability index (Pearson's correlation coefficient of 0.78, p value 0.023). The C9orf72 hexanucleotide repeat was only found in humans, chimpanzees and gorillas, species with higher opposability indices.

CONCLUSIONS:

This may support a role of the hexanucleotide repeat in the same developmental pathways in species with higher prehensility, which may be associated with the selective vulnerability of cortico-motoneuronal cells in humans, manifested most obviously as the 'split hand' syndrome in ALS.

KEYWORDS:

C9orf72; cortico-motoneuronal vulnerability; thumb opposability

PMID:
28010125
PMCID:
PMC5425628
DOI:
10.1080/21678421.2016.1257024
[Indexed for MEDLINE]
Free PMC Article

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