Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia |
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| Authors: | Nicole Weisschuh Katarina Stingl Isabelle Audo Saskia Biskup Béatrice Bocquet Kari Branham Marie S Burstedt Elfride De Baere Meindert J De Vries Irina Golovleva Andrew Green John Heckenlively Bart P Leroy Isabelle Meunier Elias Traboulsi Bernd Wissinger Susanne Kohl |
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| Affiliation: | 1. Institute for Ophthalmic Research, Centre for Ophthalmology, University Tuebingen, Tuebingen, Germany;2. Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut 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. Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan;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, Childrens' 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, Dublin, Ireland;14. Ophthalmic Genetics & Visual Electrophysiology, Division of Ophthalmology & Center for Cellular & Molecular Therapy, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;15. Department of Ophthalmology, Ghent University Hospital & Ghent University, Ghent, Belgium;16. Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio |
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| Abstract: | 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 preselected 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 1,074 independent families. |
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| Keywords: | achromatopsia cone phosphodiesterase mutation spectrum and prevalence PDE6C |
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