Genetic testing in patients with retinitis pigmentosa
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Genetic testing in patients with retinitis pigmentosa : Features of unsolved cases. / Birtel, Johannes; Gliem, Martin; Oishi, Akio; Müller, Philipp L; Herrmann, Philipp; Holz, Frank G; Mangold, Elisabeth; Knapp, Michael; Bolz, Hanno J; Charbel Issa, Peter.
in: CLIN EXP OPHTHALMOL, Jahrgang 47, Nr. 6, 08.2019, S. 779-786.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genetic testing in patients with retinitis pigmentosa
T2 - Features of unsolved cases
AU - Birtel, Johannes
AU - Gliem, Martin
AU - Oishi, Akio
AU - Müller, Philipp L
AU - Herrmann, Philipp
AU - Holz, Frank G
AU - Mangold, Elisabeth
AU - Knapp, Michael
AU - Bolz, Hanno J
AU - Charbel Issa, Peter
N1 - © 2019 Royal Australian and New Zealand College of Ophthalmologists.
PY - 2019/8
Y1 - 2019/8
N2 - IMPORTANCE: Uncommon characteristics in genetically unsolved retinitis pigmentosa (RP) patients may indicate an incorrect clinical diagnosis or as yet unknown genetic causes resulting in specific retinal phenotypes. The diagnostic yield of targeted next-generation sequencing may be increased by a reasonable preselection of RP-patients.BACKGROUND: To systematically evaluate and compare features of genetically solved and unsolved RP-patients.DESIGN: Retrospective, observational study.PARTICIPANTS: One-hundred and twelve consecutive RP-patients who underwent extensive molecular genetic analysis.METHODS: Characterization of patients based on multimodal imaging and medical history.MAIN OUTCOME MEASURES: Differences between genetically solved and unsolved RP-patients.RESULTS: Compared to genetically solved patients (n = 77), genetically unsolved patients (n = 35) more frequently had an age of disease-onset above 30 years (60% vs 8%; P < 0.0001), showed atypical fundus features (49% vs 8%; P < 0. 0001) and indicators for phenocopies (eg, autoimmune diseases) (17% vs 0%; P < 0. 001). Evidence for a particular inheritance pattern was less common (20% vs 49%; P < 0. 01). The diagnostic yield was 84% (71/85) in patients with first symptoms below 30 years-of-age, compared to 69% (77/112) in the overall cohort. The other selection criteria alone or in combination resulted in limited further increase of the diagnostic yield (up to 89%) while excluding considerably more patients (up to 56%) from genetic testing.CONCLUSIONS AND RELEVANCE: The medical history and retinal phenotype differ between genetically solved and a subgroup of unsolved RP-patients, which may reflect undetected genotypes or retinal conditions mimicking RP. Patient stratification may inform on the individual likelihood of identifying disease-causing mutations and may impact patient counselling.
AB - IMPORTANCE: Uncommon characteristics in genetically unsolved retinitis pigmentosa (RP) patients may indicate an incorrect clinical diagnosis or as yet unknown genetic causes resulting in specific retinal phenotypes. The diagnostic yield of targeted next-generation sequencing may be increased by a reasonable preselection of RP-patients.BACKGROUND: To systematically evaluate and compare features of genetically solved and unsolved RP-patients.DESIGN: Retrospective, observational study.PARTICIPANTS: One-hundred and twelve consecutive RP-patients who underwent extensive molecular genetic analysis.METHODS: Characterization of patients based on multimodal imaging and medical history.MAIN OUTCOME MEASURES: Differences between genetically solved and unsolved RP-patients.RESULTS: Compared to genetically solved patients (n = 77), genetically unsolved patients (n = 35) more frequently had an age of disease-onset above 30 years (60% vs 8%; P < 0.0001), showed atypical fundus features (49% vs 8%; P < 0. 0001) and indicators for phenocopies (eg, autoimmune diseases) (17% vs 0%; P < 0. 001). Evidence for a particular inheritance pattern was less common (20% vs 49%; P < 0. 01). The diagnostic yield was 84% (71/85) in patients with first symptoms below 30 years-of-age, compared to 69% (77/112) in the overall cohort. The other selection criteria alone or in combination resulted in limited further increase of the diagnostic yield (up to 89%) while excluding considerably more patients (up to 56%) from genetic testing.CONCLUSIONS AND RELEVANCE: The medical history and retinal phenotype differ between genetically solved and a subgroup of unsolved RP-patients, which may reflect undetected genotypes or retinal conditions mimicking RP. Patient stratification may inform on the individual likelihood of identifying disease-causing mutations and may impact patient counselling.
KW - Adult
KW - Electroretinography
KW - Female
KW - Genetic Testing
KW - High-Throughput Nucleotide Sequencing
KW - Humans
KW - Male
KW - Middle Aged
KW - Phenotype
KW - Retinitis Pigmentosa/diagnosis
KW - Retrospective Studies
KW - Tomography, Optical Coherence
KW - Visual Acuity/physiology
KW - Visual Fields/physiology
U2 - 10.1111/ceo.13516
DO - 10.1111/ceo.13516
M3 - SCORING: Journal article
C2 - 30977268
VL - 47
SP - 779
EP - 786
JO - CLIN EXP OPHTHALMOL
JF - CLIN EXP OPHTHALMOL
SN - 1442-6404
IS - 6
ER -