Next generation gene testing

Effective in detecting complicated HSP


Whole-exome genetic sequencing is found to be a cost-effective diagnostic tool for complicated HSP.


Hereditary spastic paraplegias constitute a heterogeneous group of neurodegenerative diseases encompassing pure and complicated forms, for which at least 52 loci and 31 causative genes have been identified. Although mutations in the SPAST gene explain approximately 40% of the pure autosomal dominant forms, molecular diagnosis can be challenging for the sporadic and recessive forms, which are often complicated and clinically overlap with a broad number of movement disorders.

The validity of exome sequencing as a routine diagnostic approach in the movement disorder clinic needs to be assessed. The main goal of this study was to explore the usefulness of an exome analysis for the diagnosis of a complicated form of spastic paraplegia.

Whole-exome sequencing was performed in two Spanish siblings with a neurodegenerative syndrome including upper and lower motor neuron, ocular and cerebellar signs. Exome sequencing revealed that both patients carry a novel homozygous nonsense mutation in exon 15 of the SPG11 gene (c.2678G>A; p.W893X), which was not found in 584 Spanish control chromosomes.

After many years of follow-up and multiple time-consuming genetic testing, we were able to diagnose these patients by making use of whole-exome sequencing, showing that this is a cost-efficient diagnostic tool for the movement disorder specialist.


SOURCE:  Clin Genet. 2013 Feb 25. doi: 10.1111/cge.12133. [Epub ahead of print]  © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.  PMID: 23438842 [PubMed – as supplied by publisher]

Exome sequencing is a useful diagnostic tool for complicated forms of hereditary spastic paraplegia.

Bettencourt C, López-Sendón J, García-Caldentey J, Rizzu P, Bakker I, Shomroni O, Quintáns B, Dávila J, Bevova M, Sobrido MJ, Heutink P, de Yébenes J.

Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal; Center of Research in Natural Resources (CIRN) and Department of Biology, University of the Azores, Ponta Delgada, Portugal.


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