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Neurological Sciences

, Volume 38, Issue 12, pp 2203–2207 | Cite as

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. 

Notes

Acknowledgements

The authors are grateful to the family for participating in this study. This work was supported by the grants of Scientific Research Projects Coordination Unit of Istanbul University, the Scientific and Technological Research Council of Turkey (TUBITAK), and the Republic of Turkey Ministry of Development with grant reference numbers of ONAP-11021, UEKAE, BILGEM K030-T439, and Infrastructure Grant-2011 K120020, respectively. Biobanking support was given by Istanbul Development Agency (Project Number TR10/15/YNK/0093). EY and OO have been fellows of TUBITAK Project Number 113S331.

We highly appreciate the efforts of Monica Ann Malt, MSN, RN, and CPAN (Bezmialem Vakif University, Turkey) in language editing of this paper.

Compliance with ethical standards

The authors declare no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Istanbul University, Istanbul Faculty of Medicine, Clinical Ethics Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Accordingly, informed consents were obtained from all family members.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by the grants of Scientific Research Projects Coordination Unit of Istanbul University, the Scientific and Technological Research Council of Turkey (TUBITAK), and the Republic of Turkey Ministry of Development with grant reference numbers of ONAP-11021, UEKAE, BILGEM K030-T439, and Infrastructure Grant-2011 K120020, respectively. Biobanking support was given by Istanbul Development Agency (Project Number TR10/15/YNK/0093). EY and OO have been fellows of TUBITAK Project Number 113S331.

Supplementary material

10072_2017_3049_MOESM1_ESM.docx (34 kb)
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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