title: Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing.
abstract: Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes.
authors.affiliation: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Weisschuh
authors.affiliation: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Anja K
authors.initials: AK
authors.lastname: Mayer
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum Muenchen, Neuherberg, Germany.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.affiliation: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.affiliation: CeGaT GmbH, Tuebingen, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Glöckle
authors.affiliation: Institute of Medical Genetics and Human Genetics, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Schubach
authors.affiliation: Department of Ophthalmology, Lund University, Lund, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Andreasson
authors.affiliation: University Eye Hospital, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Bernd
authors.affiliation: The Retina Foundation of the Southwest, Dallas, Texas, United States of America.
authors.forename: David G
authors.initials: DG
authors.lastname: Birch
authors.affiliation: Genetic Sensory Diseases, CHU de Montpellier, Montpellier, France.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Heckenlively
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.affiliation: Department of Ophthalmology, Lund University, Lund, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Kamme
authors.affiliation: Rare Retinal Disease Center, AugenZentrum Siegburg, MVZ ADTC Siegburg GmbH, Siegburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kellner
authors.affiliation: Institute of Human Genetics, Julius-Maximilian-University, Wuerzburg, Germany.
authors.forename: Erdmute
authors.initials: E
authors.lastname: Kunstmann
authors.affiliation: Department of Medicine, University Hospital of Padua, Padua, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Maffei
authors.affiliation: Eye Center, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Reiff
authors.affiliation: Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohrschneider
authors.affiliation: National Eye Clinic, Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.affiliation: University Eye Hospital, Ludwig Maximilians University, Munich, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Rudolph
authors.affiliation: Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Vámos
authors.affiliation: Department of Ophthalmology, Semmelweis University, Budapest, Hungary.|Department of Ophthalmology, University of Pécs Medical School, Pécs, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Varsányi
authors.affiliation: Casey Eye Institute, Oregon Retinal Degeneration Center, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
authors.affiliation: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
mesh_terms: D056915:DNA Copy Number Variations; D059472:Exome; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D059645:Mutation Rate; D010375:Pedigree; D010641:Phenotype; D058499:Retinal Dystrophies / Q000175:diagnosis / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C454222:PRPF31 protein, human; C099929:RPGR protein, human