76 HSP types from 59 genes … and counting

Posted - September 2015 in Research Highlights

Gene testing advances show complex picture

 

As at June 2015, 76 different types of HSP involving a myriad of genetic mutations in 59 genes have been discovered and described.

 

Next Generation Sequencing genetic testing technology has enabled these discoveries and together with clinical examination has revealed overlaps in both genes and symptom profiles (phenotypes) with other neurodegenerative and neurodevelopmental disorders including neuropathies, cerebellar ataxias and intellectual disability.

 

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Abstract

Hereditary spastic paraplegias (HSPs) are genetically determined neurodegenerative disorders characterized by progressive weakness and spasticity of lower limbs, and are among the most clinically and genetically heterogeneous human diseases. All modes of inheritance have been described, and the recent technological revolution in molecular genetics has led to the identification of 76 different spastic gait disease-loci with 59 corresponding spastic paraplegia genes.

 

Autosomal recessive HSPs are usually associated with diverse additional features (referred to as complicated forms), contrary to autosomal dominant HSPs, which are mostly pure. However, the identification of additional mutations and families has considerably enlarged the clinical spectra, and has revealed a huge clinical variability for almost all HSP. Complicated forms have also been described for primary pure HSP subtypes, adding further complexity to the genotype-phenotype correlations.

 

In addition, the introduction of next generation sequencing in clinical practice has revealed a genetic and phenotypic overlap with other neurodegenerative disorders (amyotrophic lateral sclerosis, neuropathies, cerebellar ataxias, etc.) and neurodevelopmental disorders, including intellectual disability.

 

This review aims to describe the most recent advances in the field and to provide genotype-phenotype correlations that could help clinical diagnoses of this heterogeneous group of disorders.

 

SOURCE: Rev Neurol (Paris). 2015 Jun-Jul;171(6-7):505-30. doi: 10.1016/j.neurol.2015.02.017. Epub 2015 May 23. Copyright © 2015 Elsevier Masson SAS. All rights reserved. PMID: 26008818 [PubMed – in process]

 

Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting.

 

Klebe S1, Stevanin G2, Depienne C3.

  • 1Department of neurology, university hospital Würzburg, Josef-Schneider-Straße 11, 97080 Würzburg, Germany.
  • 2Sorbonne universités, UPMC université Paris 06, 91-105, boulevard de l’Hôpital, 75013 Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, 47/83, boulevard de l’Hôpital, 75013 Paris, France; École pratique des hautes études, 4-14, rue Ferrus, 75014 Paris, France; Département de génétique, AP-HP, hôpital Pitié-Salpêtrière, 47/83, boulevard de l’Hôpital, 75013 Paris, France.
  • 3Sorbonne universités, UPMC université Paris 06, 91-105, boulevard de l’Hôpital, 75013 Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, 47/83, boulevard de l’Hôpital, 75013 Paris, France; Département de génétique, AP-HP, hôpital Pitié-Salpêtrière, 47/83, boulevard de l’Hôpital, 75013 Paris, France. Electronic address: [email protected]

 

Comments on this story

  1. Angela posted at 9:27 pm on 2 September 2015Reply

    Hi there I had gene testing approx. 18 months – 2 years ago at Alfred Hospital Melbourne
    they could not identify my gene does this now mean that if I go back to the Alfred for gene testing again they will be able to help me? Or should I be going somewhere else for this testing? Thank you

    • Editor posted at 3:18 pm on 3 September 2015Reply

      Hi Angela,

      To the best of my knowledge the Alfred Hospital in Melbourne does not itself do genetic testing for HSP. Your Sample was quite possibly sent away for testing. The heading on the results form you may have received will tell you which lab did the testing and the genes tested for may be listed. One suggestion is to contact the genetic counsellor you saw and pose the question to them. They will either know, or can find out if the gene panel at the particular lab has been expanded in the last two years and if the extra genes now included for testing may be candidates in your particular case given data such as your family history and clinical features of your HSP. Then both you and they will be in a better position to decide if and when further testing makes sense, and to also factor into the decision any extra costs that may be involved.

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