Posted - June 2015 in Research Highlights
More complex picture has become evident
Emerging findings suggest the need for a revised classification of the spastic paraplegias that better reflects what is now known.
As the amount of research on the different forms of HSP increases and expands, and as ever more sophisticated genetic detection and testing is employed, the current classification system for the HSPs now appears somewhat limited. Clinical and genetic relationships between the HSPs and other neurodegenerative conditions are being established, blurring the demarcations between them. Increasing variability in HSP symptoms, age of onset and progression within some HSP types are now regularly being found, as well as different modes of inheritance, where previously just one mode was thought to occur for a given type.
Hereditary spastic paraplegias (HSP) are rare neurodegenerative diseases sharing the degeneration of the corticospinal tracts as the main pathological characteristic. They are considered one of the most heterogeneous (variable rather than uniform) neurological disorders.
All modes of inheritance have been described for the 84 different loci and 67 known causative genes implicated up to now. Recent advances in molecular genetics have revealed clinico-genetic heterogeneity of these disorders including their clinical and genetic overlap with other diseases of the nervous system.
The systematic analysis of a large set of genes, including exome sequencing, is unmasking unusual phenotypes or inheritance modes associated with mutations in HSP genes and related genes involved in various neurological diseases. A new nosology (disease classification) may emerge after integration and understanding of these new data to replace the current classification.
Collectively, functions of the known genes implicate the disturbance of intracellular membrane dynamics and trafficking as the consequence of alterations of cytoskeletal dynamics, lipid metabolism and organelle structures, which represent in fact a relatively small number of cellular processes that could help to find common curative approaches, which are still lacking.
SOURCE: Hum Genet. 2015 Mar 11. [Epub ahead of print] PMID: 25758904 [PubMed – as supplied by publisher]
Delving into the complexity of hereditary spastic paraplegias: how unexpected phenotypes and inheritance modes are revolutionizing their nosology.
Tesson C1, Koht J, Stevanin G.
1 INSERM U1127, CNRS UMR7225, Sorbonne Universités, UPMC Univ Paris 06 UMR_S1127, EPHE, Institut du Cerveau et de la Moelle épinière, CHU Pitié-Salpêtrière, 47 bd de l’Hôpital, 75013, Paris, France.