Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia
| Autor: | John R. Heckenlively, Elfride De Baere, Nicole Weisschuh, Marie Burstedt, Meindert De Vries, Katarina Stingl, Saskia Biskup, Bernd Wissinger, Isabelle Meunier, Andrew R Green, Isabelle Audo, Kari Branham, Irina Golovleva, Bart P. Leroy, Elias I. Traboulsi, Susanne Kohl, Béatrice Bocquet |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Achromatopsia Genotype Color Vision Defects Biology medicine.disease_cause DNA sequencing 03 medical and health sciences symbols.namesake 0302 clinical medicine Catalytic Domain Databases Genetic Genetics medicine Humans Genetic Predisposition to Disease Allele Eye Proteins Gene Alleles Genetic Association Studies Genetics (clinical) Sanger sequencing Cyclic Nucleotide Phosphodiesterases Type 6 Mutation Infant Newborn Computational Biology Infant Sequence Analysis DNA medicine.disease Phenotype 030104 developmental biology Child Preschool RNA splicing Retinal Cone Photoreceptor Cells 030221 ophthalmology & optometry symbols sense organs Visual phototransduction |
| Zdroj: | Human Mutation. 39:1366-1371 |
| ISSN: | 1059-7794 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text