Hereditary ataxias and paraparesias: clinical and genetic update.

Livia Parodi, Giulia Coarelli, Giovanni Stevanin, Alexis Brice, Alexandra Durr
Current Opinion in Neurology. 2018-08-01; 31(4): 462-471
DOI: 10.1097/wco.0000000000000585

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1. Curr Opin Neurol. 2018 Aug;31(4):462-471. doi: 10.1097/WCO.0000000000000585.

Hereditary ataxias and paraparesias: clinical and genetic update.

Parodi L(1), Coarelli G(1)(2), Stevanin G(1)(3), Brice A(1), Durr A(1)(4).

Author information:
(1)Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS UMR
7225, Sorbonne, Université, Paris.
(2)Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Neurology,
Avicenne Hospital, University Paris 13, Bobigny.
(3)EPHE, PSL Research University.
(4)Assistance Publique-Ho[Combining Circumflex Accent]pitaux de Paris (AP-HP),
Genetic Department, Pitié-Salpêtrière University Hospital, Paris, France.

PURPOSE OF REVIEW: This review aims at updating the clinical and genetic aspects
of hereditary spastic paraplegias (HSPs) and hereditary cerebellar ataxias
(HCAs), focusing on the concept of spastic-ataxia phenotypic spectrum and on
newly identified clinical overlaps with other neurological and nonneurological
RECENT FINDINGS: Next-generation sequencing (NGS) has allowed the discovery of
new genes involved in HSPs and HCAs. They include new HCAs genes such as GRM1
(SCA44), FAT2 (SCA45), PLD3 (SCA46), SCYL1 (SCAR21), UBA5 (SCAR24) and XRCC1
(SCAR26) as well as CAPN1 (SPG76) and CPT1C (SPG73) in HSPs. Furthermore, NGS
allowed enriching known genes phenotype, reinforcing the overlap between HSPs and
HCAs defining the spastic ataxia spectrum. Clear examples are the expanded
phenotypes associated with mutations in SPG7, PNPLA6, GBA2, KIF1C, CYP7B1, FA2H,
ATP13A2 and many others. Moreover, other genes not previously linked to HCAs and
HSPs have been implicated in spastic or ataxic phenotypes.
SUMMARY: The increase of HSPs and HCAs-related phenotypes and the continuous
discovery of genes complicate clinical diagnostic in practice but, at the same
time, it helps highlighting common pathological pathways, therefore opening new
ways to the development of common therapeutic approaches.

DOI: 10.1097/WCO.0000000000000585
PMID: 29847346 [Indexed for MEDLINE]

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