Amplifying the spectrum of SPAST gene mutations

Amplifying the spectrum of SPAST gene mutations

Authors

  • Lorenzo Verriello Neurology Unit, Department of Neurosciences, Santa Maria della Misericordia University Hospital, ASUFC, Udine, Italy
  • Incoronata Renata Lonigro Institute of Clinical Pathology, Santa Maria della Misericordia University Hospital, ASUFC, Udine, Italy
  • Maria Elena Pessa a:1:{s:5:"en_US";s:49:"Azienda ospedaliero universitaria Friuli centrale";}
  • Elena Betto Institute of Clinical Pathology, Santa Maria della Misericordia University Hospital, ASUFC, Udine, Italy
  • Giada Pauletto Neurology Unit, Department of Neurosciences, Santa Maria della Misericordia University Hospital, ASUFC, Udine, Italy
  • Federico Fogolari Department of Mathematics, Informatics and Physics (DMIF), University of Udine, Italy
  • Gian Luigi Gigli Clinical Neurology Unit, Department of Neurosciences, Santa Maria della Misericordia University Hospital, ASUFC, Udine, Italy
  • Francesco Curcio Institute of Clinical Pathology, Santa Maria della Misericordia University Hospital, ASUFC, Udine, Italy

Keywords:

SPAST gene, hereditary spastic paraplegia, spastin

Abstract

Hereditary spastic paraplegias (HSPs) include a group of neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities, caused by axon degeneration of corticospinal tracts. Spastic paraplegia type 4 (SPG4) is the most common autosomal dominant form of HSP and is caused by mutations in the SPAST gene.

SPAST gene encodes for the protein spastin, a member of the ATPases Associated with a variety of cellular Activity (AAA) family.We describe a newly variant in SPAST gene, within an Italian family affected by pure HSP. In particular, we found a heterozygous intragenic microdeletion of 3T in exon 13 of SPG4 gene. The 3T deletion results in a mutated protein with a unique leucine residues deletion at the protein position 508, in the AAA ATPase domain. This variant is not registered in any public database either as rare normal variant nor as mutation in SPAST gene and the importance of this aminoacid is confirmed by the absolute conservation in multiple alignments with diverse species. We conclude that the novel SPAST gene variant identified is probably pathogenic and destabilizes the precise arrangement of the nucleotide binding domain, with a consequent loss-of-function of the mutated spastin protein. 

References

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Published

04-11-2021

Issue

Section

Case Reports: General Surgery and Miscellanea

How to Cite

1.
Verriello L, Lonigro IR, Pessa ME, Betto E, Pauletto G, Fogolari F, et al. Amplifying the spectrum of SPAST gene mutations. Acta Biomed [Internet]. 2021 Nov. 4 [cited 2024 Jul. 22];92(S1):e2021220. Available from: https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/11608