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Clinical and molecular studies in two new cases of ARSACS

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Abstract

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.

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Funding

This study was partially supported by the Foundation de l’Ataxie Charlevoix-Saguenay (www.arsacs.com) 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).

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Author notes

  1. Ivana Ricca and Federica Morani contributed equally to this work.

Authors and Affiliations

  1. Molecular Medicine, IRCCS Fondazione Stella Maris, via dei Giacinti 2 Calambrone, 56128, Pisa, Italy

    Ivana Ricca, Federica Morani, Claudia Nesti, Alessandra Tessa & Filippo Maria Santorelli

  2. Pediatric Ophthalmology Unit, Meyer Children’s Hospital, University of Florence, Florence, Italy

    Giacomo Maria Bacci & Roberto Caputo

Authors
  1. Ivana Ricca
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  2. Federica Morani
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  3. Giacomo Maria Bacci
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  4. Claudia Nesti
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  5. Roberto Caputo
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  6. Alessandra Tessa
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  7. Filippo Maria Santorelli
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Correspondence to Filippo Maria Santorelli.

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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)

High Resolution Image (TIF 342 kb)

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Ricca, I., Morani, F., Bacci, G.M. et al. Clinical and molecular studies in two new cases of ARSACS. Neurogenetics 20, 45–49 (2019). https://doi.org/10.1007/s10048-019-00564-7

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