SYNE1 related cerebellar ataxia presents with variable phenotypes in a consanguineous family from Turkey

  • E. Yucesan
  • Sibel A. Ugur Iseri
  • B. Bilgic
  • Z. Gormez
  • B. Bakir Gungor
  • A. Sarac
  • O. Ozdemir
  • M. Sagiroglu
  • H. Gurvit
  • H. Hanagasi
  • U. Ozbek
Brief Communication

Abstract

SYNE1 related autosomal recessive cerebellar ataxia type 1 (ARCA1) is a late-onset cerebellar ataxia with slow progression originally demonstrated in French-Canadian populations of Quebec, Canada. Nevertheless, recent studies on SYNE1 ataxia have conveyed the condition from a geographically limited pure cerebellar recessive ataxia to a complex multisystem phenotype that is relatively common on the global scale. To determine the underlying genetic cause of the ataxia phenotype in a consanguineous family from Turkey presenting with very slow progressive cerebellar symptoms including dysarthria, dysmetria, and gait ataxia, we performed SNP-based linkage analysis in the family along with whole exome sequencing (WES) in two affected siblings. We identified a homozygous variant in SYNE1 (NM_033071.3: c.13086delC; p.His4362GlnfsX2) in all four affected siblings. This variant presented herein has originally been associated with only pure ataxia in a single case. We thus present segregation and phenotypic manifestations of this variant in four affected family members and further extend the pure ataxia phenotype with upper motor neuron involvement and peripheral neuropathy. Our findings in turn established a precise molecular diagnosis in this family, demonstrating the use of WES combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

Keywords

Autosomal recessive cerebellar ataxia SYNE1 Peripheral neuropathy Linkage analysis Whole exome sequencing E. Yucesan and S. A. Ugur Iseri contributed equally to this work. 

Supplementary material

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ESM 1(DOCX 33 kb)

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Copyright information

© Springer-Verlag Italia S.r.l. 2017

Authors and Affiliations

  1. 1.Department of Genetics, Aziz Sancar Institute of Experimental MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Institute of Life Sciences and Biotechnology, Bezmialem Vakif UniversityIstanbulTurkey
  3. 3.Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  4. 4.Advanced Genomics and Bioinformatics Research Center (IGBAM), BILGEM, TUBITAKKocaeliTurkey
  5. 5.Department of Software Engineering, Faculty of EngineeringIstinye UniversityIstanbulTurkey
  6. 6.Faculty of EngineeringAbdullah Gul UniversityKayseriTurkey
  7. 7.Marmara Research Center, Genetic Engineering and Biotechnology Institute, TUBITAKKocaeliTurkey
  8. 8.TUBITAK, BILGEM, UEKAEKocaeliTurkey
  9. 9.Faculty of Medicine, Department of Medical GeneticsAcıbadem UniversityIstanbulTurkey

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