neurogenetics

, 10:151

An inherited large-scale rearrangement in SACS associated with spastic ataxia and hearing loss

  • Alessandra Terracciano
  • Carlo Casali
  • Gaetano S. Grieco
  • Daniela Orteschi
  • Silvia Di Giandomenico
  • Laura Seminara
  • Roberto Di Fabio
  • Rosalba Carrozzo
  • Alessandro Simonati
  • Giovanni Stevanin
  • Marcella Zollino
  • Filippo M. Santorelli
Short Communication

DOI: 10.1007/s10048-008-0159-8

Cite this article as:
Terracciano, A., Casali, C., Grieco, G.S. et al. Neurogenetics (2009) 10: 151. doi:10.1007/s10048-008-0159-8

Abstract

Autosomal recessive spastic ataxia of Charlevoix–Saguenay is a neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy, with or without mental retardation. The array of mutations in SACS has expanded worldwide after the first description in Quebec. We herein report the identification of an unconventional SACS mutation, a large-scale deletion sized ∼1.5 Mb encompassing the whole gene, in two unrelated patients. The clinical phenotype of the patients was similar to more canonical ARSACS cases, though it is was complicated by the unusual presence of hearing loss. Our findings suggest that a “microdeletion” on chromosome 13q12 represents a novel allelic variant associated with ARSACS, stressing the need for an expanded testing in molecular diagnostic laboratories.

Keywords

Array CGH ARSACS Chromosomal deletion 

Supplementary material

10048_2008_159_MOESM1_ESM.doc (24 kb)
E-Figure 1a Electropherogram of the sequences flanking the SACS exon 7 in a normal control (a) and in patient 1-LF who harbored the c.600_604+1delAACAGG/p.I202fsX6 mutation (b) at the exon–intron junction. The deleted region is boxed. b Electropherogram of the sequences flanking the SACS exon 10 in patient 2-MPG harboring the c.7302T>C/p.Leu2374Ser mutation (arrow). c Fluorescent in situ hybridization (FISH) in patient 1-LF. A representative metaphase image is shown. Probe RP11-72P19 was labeled with spectrum Orange (Vysis, red in this figure), whereas the chromosome 13q-subtelomeric probe was labeled with FITCH (Vysis, green in this figure) as control. The missing red signal on chromosome 13q12 is evident (arrow). (tif 11.7 MB)
10048_2008_159_MOESM2_ESM.doc (34 kb)
E-Table 1Oligonucleotide sequences (5′–3′) of primers used for qPCR analyses and for single nucleotide polymorphism genotyping (doc 33.5 KB)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Alessandra Terracciano
    • 1
  • Carlo Casali
    • 2
  • Gaetano S. Grieco
    • 3
  • Daniela Orteschi
    • 4
  • Silvia Di Giandomenico
    • 1
  • Laura Seminara
    • 4
  • Roberto Di Fabio
    • 2
  • Rosalba Carrozzo
    • 1
  • Alessandro Simonati
    • 5
  • Giovanni Stevanin
    • 6
  • Marcella Zollino
    • 4
  • Filippo M. Santorelli
    • 1
  1. 1.Molecular Medicine and NeurologyIRCCS Bambino Gesù Children’s HospitalRomeItaly
  2. 2.Department of Neurology and ORLUniversity of Rome La Sapienza-Polo PontinoLatinaItaly
  3. 3.Molecular NeurogeneticsIRCCS “C. Mondino” Institute of Neurology FoundationPaviaItaly
  4. 4.Institute of Medical GeneticsCatholic UniversityRomeItaly
  5. 5.Department of Neurological and Visual SciencesUniversity of VeronaVeronaItaly
  6. 6.INSERM, UMR_S679 Neurologie & Thérapeutique ExpérimentaleUPMC Univ Paris 06, UMR_S679, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Génétique et CytogénétiqueParisFrance

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