SPG7 HSP discoveries

Posted - June 2012 in Research Highlights

Wide spectrum of HSP forms

SPG7 mutations have now been shown to be inherited both dominantly and recessively, and to be associated with both pure and complicated HSP. This research study discovered 12 new SPG 7 mutations.


Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations.


To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients.


Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions.


All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients.


Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.


SOURCE: Clinical Genetics. doi: 10.1111/j.1399-0004.2012.01896.x    © 2012 John Wiley & Sons A/S


SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V


Sánchez-Ferrero E, Coto E, Beetz C, Gámez J, Corao A, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual-Pascual SI, López de Munaín A, Garcia-Barcina MJ, Alvarez V


Laboratory of Molecular Genetics-Genetic Unit, Laboratorio de Medicina, Hospital Universitario Central de Asturias, 33006-Oviedo, Spain.



Comments on this story

  1. Leonard posted at 11:17 am on 29 November 2016Reply

    Got H.S.P. about 15 years ago started walking funny then went on to walking stick then to a walker could end up in a wheelchair very soon.

  2. Ryan posted at 6:32 am on 17 March 2018Reply

    I was diagnosed in Nov. 2017 with HSP via a homozygous, missense mutation of my SPG7 gene (c.1529C>T; p.A510V). Is there anything more known about that location other than that A510V is pathogenic?


    • Editor posted at 5:55 pm on 18 March 2018Reply

      Editor’s Note: Here is a well-catalogued and maintained reference website for the HSPs http://neuromuscular.wustl.edu/spinal/fsp.html#5c. I am unable to answer your question specifically, but more generally:
      * there is an imprecise correlation in general between HSP mutation type and phenotype (age of onset, symptom profile, rate of progression) with common occurrences of significant phenotypic variability in family members affected with the identical mutation
      * SPG7 is the subject of significantly increased research attention in recent times, being associated with a number of conditions with the link appearing to be mitochondrial impairment https://www.ncbi.nlm.nih.gov/pubmed/?term=SPG7
      * there is reason to believe that any treatment that is effective in restoring normal mitochondrial functioning in any of the HSPs where mitochondrial impairment is the relevant mechanism, may also be effective, not only with other HSPs with the same mechanism, but also perhaps with other conditions associated with mitochondrial impairment. https://hspersunite.org.au/about-hsp/understanding-hsp-mechanism/

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