Large study of SPG4 HSPers

Four major findings


This study of 118 HSPers with confirmed SPAST gene mutations that cause SPG4 HSP was a collaboration between researchers from the UK, Moldova and Italy. There are four major findings:

  • a number of new HSP causing mutations in the SPAST gene

  • a much higher rate of complex HSP (25%)

  • psychiatric disorders the most common complication (10%)

  • correlation between loss-of-function SPAST mutations and the occurrence of psychiatric disorders.


Prof Henry Houlden



The hereditary spastic paraplegias (HSPs) are a rare and heterogeneous group of neurodegenerative disorders that are clinically characterised by progressive lower limb spasticity. They are classified as either ‘pure’ or ‘complex’ where spastic paraplegia is complicated with additional neurological features. Mutations in the spastin gene (SPAST) are the most common cause of HSP and typically present with a pure form.



We assessed in detail the phenotypic and genetic spectrum of SPAST-related HSP focused on 118 patients carrying SPAST mutations.



This study, one of the largest cohorts of genetically confirmed spastin patients to date, contributes with the discovery of a significant number of novel SPAST mutations. Our data reveal a high rate of complex cases (25%), with psychiatric disorders among the most common comorbidity (10% of all SPAST patients). Further, we identify a genotype-phenotype correlation between patients carrying loss-of-function mutations in SPAST and the presence of psychiatric disorders.


SOURCE: J Neurol Neurosurg Psychiatry. 2017 Aug;88(8):681-687. doi: 10.1136/jnnp-2017-315796. Epub 2017 Jun 1. PMID: 28572275 © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.


Truncating mutations in SPAST patients are associated with a high rate of psychiatric comorbidities in hereditary spastic paraplegia.


Chelban V1,2,3, Tucci A1,2,4,5, Lynch DS1,2, Polke JM1,2,6, Santos L6, Jonvik H1,2, Groppa S3, Wood NW1,2, Houlden H1,2,6.


1 Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

2 National Hospital for Neurology and Neurosurgery, London, UK.

3 Department of Neurology and Neurosurgery, Institute of Emergency Medicine, Chisinau, Republic of Moldova.

4 Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy.

5 Department of Pathophysiology & Transplantation, Università degli Studi di Milano, Milano, Italy.

6 Neurogenetics Laboratory, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.


Your email address will not be published. Required fields are marked *