Delving into the complexity of hereditary spastic paraplegias: how unexpected phenotypes and inheritance modes are revolutionizing their nosology.
Hum Genet. 2015-03-11; 134(6): 511-538
DOI: 10.1007/s00439-015-1536-7
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1. Hum Genet. 2015 Jun;134(6):511-38. doi: 10.1007/s00439-015-1536-7. Epub 2015 Mar
11.
Delving into the complexity of hereditary spastic paraplegias: how unexpected
phenotypes and inheritance modes are revolutionizing their nosology.
Tesson C(1), Koht J, Stevanin G.
Author information:
(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.
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 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 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.
DOI: 10.1007/s00439-015-1536-7
PMCID: PMC4424374
PMID: 25758904 [Indexed for MEDLINE]