Clinical and molecular studies in two new cases of ARSACS

  • Ivana Ricca
  • Federica Morani
  • Giacomo Maria Bacci
  • Claudia Nesti
  • Roberto Caputo
  • Alessandra Tessa
  • Filippo Maria SantorelliEmail author
Short Communication


Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodevelopmental disorder characterized by the association of spastic ataxia and sensorimotor neuropathy. Additional features include retinal changes and cognitive impairment. Today, next-generation sequencing (NGS) techniques are allowing the rapid identification of a growing number of missense variants, even in less typical forms of the disease, but the pathogenic significance of these changes is often difficult to establish on the basis of classic bioinformatics criteria and genotype/phenotype correlations. Herein, we describe two novel cases of missense mutations in SACS. The two individuals were identified during the genetic screening of a large cohort of patients with inherited ataxias. We discuss how protein studies and specialized ophthalmological investigations could represent useful pointers for the interpretation of genetic data. Combination of these tools with NGS for rapid genotyping might help to identify new true ARSACS cases.


ARSACS Sacsin Genotype-phenotype correlation Mitochondrial network Retinal myelinated fibers 


Funding information

This study was partially supported by the Foundation de l’Ataxie Charlevoix-Saguenay ( to FM, the Italian Ministry of Health-Ricerca Finalizzata RF-2016-02361610 (to FMS), and the E-RARE-3 Joint Transnational Call grant “Preparing therapies for autosomal recessive ataxias” (PREPARE) (MoH; project 3398 to FMS).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10048_2019_564_Fig3_ESM.png (203 kb)
Supplementary Figure S1

Sequence electropherograms showing the heterozygous SACS variations (below) in the patients compared with their controls (above). The arrows indicate the heterozygous nucleotides in P1 and P2. The family trees are also depicted. Squares, males; circles, females; filled symbols, affected individuals; M and m indicate SACS mutations. (PNG 202 kb)

10048_2019_564_MOESM1_ESM.tif (343 kb)
High Resolution Image (TIF 342 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ivana Ricca
    • 1
  • Federica Morani
    • 1
  • Giacomo Maria Bacci
    • 2
  • Claudia Nesti
    • 1
  • Roberto Caputo
    • 2
  • Alessandra Tessa
    • 1
  • Filippo Maria Santorelli
    • 1
    Email author
  1. 1.Molecular Medicine, IRCCS Fondazione Stella MarisPisaItaly
  2. 2.Pediatric Ophthalmology Unit, Meyer Children’s HospitalUniversity of FlorenceFlorenceItaly

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