Abstract
We describe two pairs of siblings from a consanguineous family manifesting autosomal recessive hereditary spastic paraplegia caused by a novel mutation in the EXOSC3 gene, previously reported in pontocerebellar hypoplasia type 1. Clinical findings included delayed motor milestones, early-onset spastic paraplegia, variable cognitive disability, and cerebellar signs. Cerebral imaging demonstrated enlarged cisterna magna and mild hypoplasia and atrophy of the lower vermis with a normal pons. Genetic analysis using homozygosity mapping followed by whole exome sequencing identified homozygous c.571G>T; p.G191C mutation in the EXOSC3 gene. We suggest that EXOSC3 mutations may present not only as pontocerebellar hypoplasia type 1, but also as a complicated form of hereditary spastic paraplegia without pontine hypoplasia or atrophy.
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Abbreviations
- HSP:
-
Hereditary spastic paraplegia
- MRI:
-
Magnetic resonance imaging
- PCH:
-
Pontocerebellar hypoplasia
References
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Acknowledgments
This study was supported in part by the Israeli MOH grant (#5914) and the Israeli MOH/ERA-Net (#4800).
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The authors declare no conflict of interest.
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We have received consent forms from the participants in the study and have them available upon request. Approval from an ethical standards committee to conduct this study was waived.
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A. Halevy, I. Lerer, R. Straussberg, and A. Lossos contributed equally to the manuscript.
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Supplementary Fig.
Linked homozygous regions shown according to chromosomal regions using HomozygosityMapper (Seelow D, Schuelke M, Hildebrandt F, Nürnberg P. Nucleic Acids Res. 2009 May 21). Arrow marks shared region encompassing EXOSC3 mutation and star depicts a smaller shared region on chromosome 9 discussed in the main text. Supplementary material 1 (JPEG 49 kb)
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Halevy, A., Lerer, I., Cohen, R. et al. Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia. J Neurol 261, 2165–2169 (2014). https://doi.org/10.1007/s00415-014-7457-x
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DOI: https://doi.org/10.1007/s00415-014-7457-x