Panel-Based Population Next-Generation Sequencing for Inherited Retinal Degenerations.
Inherited retinopathies affect approximately two and a half million people globally, yet the majority of affected patients lack clear genetic diagnoses given the diverse range of genes and mutations implicated in these conditions. We present results from a next-generation sequencing study of a large inherited retinal disease patient population, with the goal of providing clear and actionable genetic diagnoses. Targeted sequencing was performed on 539 individuals from 309 inherited retinal disease pedigrees. Causative mutations were identified in the majority (57%, 176/309) of pedigrees. We report the association of many previously unreported variants with retinal disease, as well as new disease phenotypes associated with known genes, including the first association of the SLC24A1 gene with retinitis pigmentosa. Population statistics reporting the genes most commonly implicated in retinal disease in the cohort are presented, as are some diagnostic conundrums that can arise during such studies. Inherited retinal diseases represent an exemplar group of disorders for the application of panel-based next-generation sequencing as an effective tool for detection of causative mutations.
School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
Matthew
M
Carrigan
Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin, Ireland.
Emma
E
Duignan
Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin, Ireland.
Conor P G
CP
Malone
Mater Misericordiae University Hospital, Dublin, Ireland.
Kirk
K
Stephenson
Mater Misericordiae University Hospital, Dublin, Ireland.
Tahira
T
Saad
School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
Ciara
C
McDermott
Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
Andrew
A
Green
Mater Misericordiae University Hospital, Dublin, Ireland.
David
D
Keegan
School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
Peter
P
Humphries
School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.|Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin, Ireland.
Paul F
PF
Kenna
School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
G Jane
GJ
Farrar
D000328:Adult; D000368:Aged; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D019831:Sodium-Calcium Exchanger / Q000235:genetics*
D005136:Eye Proteins; D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger