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Primary Coenzyme Q deficiency Due to Novel ADCK3 Variants, Studies in Fibroblasts and Review of Literature

  • Adel ShalataEmail author
  • Michael Edery
  • Clair Habib
  • Jacob Genizi
  • Mohammad Mahroum
  • Lama Khalaily
  • Nurit Assaf
  • Idan Segal
  • Hoda Abed El Rahim
  • Hana Shapira
  • Danielle Urian
  • Shay Tzur
  • Liza Douiev
  • Ann SaadaEmail author
Original Paper

Abstract

Primary deficiency of coenzyme Q10 (CoQ10 ubiquinone), is classified as a mitochondrial respiratory chain disorder with phenotypic variability. The clinical manifestation may involve one or multiple tissue with variable severity and presentation may range from infancy to late onset. ADCK3 gene mutations are responsible for the most frequent form of hereditary CoQ10 deficiency (Q10 deficiency-4 OMIM #612016) which is mainly associated with autosomal recessive spinocerebellar ataxia (ARCA2, SCAR9). Here we provide the clinical, biochemical and genetic investigation for unrelated three nuclear families presenting an autosomal form of Spino-Cerebellar Ataxia due to novel mutations in the ADCK3 gene. Using next generation sequence technology we identified a homozygous Gln343Ter mutation in one family with severe, early onset of the disease and compound heterozygous mutations of Gln343Ter and Ser608Phe in two other families with variable manifestations. Biochemical investigation in fibroblasts showed decreased activity of the CoQ dependent mitochondrial respiratory chain enzyme succinate cytochrome c reductase (complex II + III). Exogenous CoQ slightly improved enzymatic activity, ATP production and decreased oxygen free radicals in some of the patient’s cells. Our results are presented in comparison to previously reported mutations and expanding the clinical, molecular and biochemical spectrum of ADCK3 related CoQ10 deficiencies.

Keywords

Spinocerebellar ataxia Q10 deficiency-4 SCAR9 Coenzyme Q ADCK3 Mitochondrial disease 

Notes

Acknowledgements

AS is supported by the Pakula family, via the American Friends of the Hebrew University of Jerusalem. The molecular genetics evaluation is supported by Ginatuna Association, Sakhnin City, POB 1115, Israel.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Simon Winter Institute for Human GeneticsBnai Zion Medical CenterHaifaIsrael
  2. 2.Clalit Health Care-Haifa and West Galilee DistrictHaifaIsrael
  3. 3.Ginatuna AssociationSakhninIsrael
  4. 4.Department of Genetic and Metabolic Diseases, Monique and Jacques Roboh Department of Genetic ResearchHadassah Medical CenterJerusalemIsrael
  5. 5.Department of PediatricsBnai Zion Medical CenterHaifaIsrael
  6. 6.Pediatric Neurology UnitBnai Zion Medical CenterHaifaIsrael
  7. 7.Bruce and Ruth Rappaport Faculty of MedicineTechnionHaifaIsrael
  8. 8.Child Development CenterClalit Health CareCarmielIsrael
  9. 9.Neurology DepartmentSchneider Children HospitalPetah TikvaIsrael
  10. 10.Laboratory of Molecular Medicine, Rappaport Faculty of Medicine and Research InstituteTechnion - Israel Institute of TechnologyHaifaIsrael
  11. 11.Genomic Research DepartmentEmedgene TechnologiesTel AvivIsrael
  12. 12.Faculty of MedicineHebrew University of JerusalemJerusalemIsrael

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