Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia.

Weisschuh N1, Stingl K1, Audo I2,3, Biskup S4, Bocquet B5,6, Branham K7, Burstedt MS8, De Baere E9, De Vries MJ10, Golovleva I11, Green A12,13, Heckenlively J7, Leroy BP9,14,15, Meunier I5,6, Traboulsi E16, Wissinger B1, Kohl S1.
  1. Institute for Ophtalmic Research, Centre for Ophtalmology, University of Tuebingen, Tuebingen, Germany.
  2. Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institu de la Vision, Paris, France.
  3. CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France.
  4. CeGaT GmbH and Praxis fuer Humangenetik Tuebingen, Tuebingen, Germany.
  5. Institute for Neurosciences of Montpellier INSERM U1051, University of Montpellier, Montpellier, France.
  6. National Center for Rare Genetic Retinal Dystrophies, Hopital Gui de Chauliac, Montpellier, France.
  7. University of Michigan Department of Ophthalmology and Visual Sciences, Ann Arbor, Michigan, United States.
  8. Department of Clinical Sciences/Ophthalmology, University of Umea, Umea, Sweden.
  9. Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
  10. Department of Ophthalmology, Children’s Hospital Queen Fabiola (Huderf), Brussels, Belgium.
  11. Department of Medical Biosciences/Medical and Clinical Genetics, University of Umea, Umea, Sweden.
  12. Department of Clinical Genetics, Our Lady’s Hospital, Crumlin, Dublin, Ireland.
  13. School of Medicine and Medical Science, University College Dublin.
  14. Ophthalmic Genetics & Visual Electrophysiology, Division of Ophthalmology & Center for Cellular & Molecular Therapy, The Children’s Hospital of Philadelphia, USA.
  15. Department of Ophthalmology, Ghent Univeristy Hospital & Ghent University, Ghent. Belgium.
  16. Cole Eye Institute, Cleveland Clinic, Cleveland, USA.


Biallelic PDE6C mutations are a known cause for rod monochromacy, better known as autosomal recessive achromatopsia (ACHM), and early-onset cone photoreceptor dysfunction. PDE6C encodes the catalytic α´-subunit of the cone photoreceptor phosphodiesterase, thereby constituting an essential part of the phototransduction cascade. Here, we present the results of a study comprising 176 genetically pre-selected patients who remained unsolved after Sanger sequencing of the most frequent genes accounting for ACHM, and were subsequently screened for exonic and splice site variants in PDE6C applying a targeted next generation sequencing approach. We were able to identify potentially pathogenic biallelic variants in 15 index cases. The mutation spectrum comprises 18 different alleles, 15 of which are novel. Our study significantly contributes to the mutation spectrum of PDE6C and allows for a realistic estimate of the prevalence of PDE6C mutations in ACHM since our entire ACHM cohort comprises 1074 independent families. This article is protected by copyright. All rights reserved.