For the Databases in Neurogenetics Special Issue
Revisiting genotype–phenotype overlap in neurogenetics: Triplet-repeat expansions mimicking spastic paraplegias†
Article first published online: 16 JUL 2012
© 2012 Wiley Periodicals, Inc.
Special Issue: Databases in Neurogenetics
Volume 33, Issue 9, pages 1315–1323, September 2012
How to Cite
Bettencourt, C., Quintáns, B., Ros, R., Ampuero, I., Yáñez, Z., Pascual, S. I., de Yébenes, J. G. and Sobrido, M.-J. (2012), Revisiting genotype–phenotype overlap in neurogenetics: Triplet-repeat expansions mimicking spastic paraplegias. Hum. Mutat., 33: 1315–1323. doi: 10.1002/humu.22148
- Issue published online: 13 AUG 2012
- Article first published online: 16 JUL 2012
- Accepted manuscript online: 29 JUN 2012 11:37AM EST
- Manuscript Accepted: 6 JUN 2012
- Manuscript Received: 8 FEB 2012
- Economía de Industria, Xunta de Galicia. Grant Number: 10PXIB9101280PR
- CIBERER intramural grant
- Ministerio de Economía y Competitividad—Gobierno de España. Grant Number: AIB2010PT-00182
- Fundação para a Ciência e a Tecnologia—FCT (Portugal). Grant Number: SFRH/BPD/63121/2009 to C.B.
- Institute of Health Carlos III (Spain) and FEDER funds (to B.Q and M.J.S)
- Fundación Carolina (Spain) and the Simón Bolívar University, Barranquilla (Colombia) (to ZY)
- triplet-repeat expansions;
- mimicked phenotypes;
- clinical overlap;
- molecular diagnosis
Hereditary spastic paraplegias (HSPs) constitute a heterogeneous group of neurological disorders, characterized primarily by progressive spasticity and weakness of the lower limbs. HSPs are caused by mutations in multiple genes (at least 48 loci and 28 causative genes). The clinical spectrum of HSPs is wide and important differences have been reported between patients with distinct mutations in the same gene, or even between different family members bearing the same mutation. Many patients with HSP present clinical deficits related to the involvement of neuronal systems other than corticospinal tracts, namely, peripheral nerves, sensory, or cerebellar pathways. These cases may be difficult to differentiate from other neurological diseases (e.g., hereditary ataxias), also genetically and clinically heterogeneous. As an illustration of how overlapping this genotype–phenotype relationship is, and the difficulties that it brings upon the development of neurogenetic algorithms and databases, we review the main clinical and genetic features of HSPs, and summarize reports on cases of triplet-repeat spinocerebellar ataxias that can mimic HSP phenotypes. This complex scenario makes the necessity of high-quality, curated mutation databases even more urgent, in order to develop adequate diagnostic guidelines, correct interpretation of genetic testing, and appropriate genetic counseling. Hum Mutat 33:1315–1323, 2012. © 2012 Wiley Periodicals, Inc.