Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy
Standard
Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy. / Birtel, Johannes; Eisenberger, Tobias; Gliem, Martin; Müller, Philipp L; Herrmann, Philipp; Betz, Christian; Zahnleiter, Diana; Neuhaus, Christine; Lenzner, Steffen; Holz, Frank G; Mangold, Elisabeth; Bolz, Hanno J; Charbel Issa, Peter.
in: SCI REP-UK, Jahrgang 8, Nr. 1, 19.03.2018, S. 4824.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy
AU - Birtel, Johannes
AU - Eisenberger, Tobias
AU - Gliem, Martin
AU - Müller, Philipp L
AU - Herrmann, Philipp
AU - Betz, Christian
AU - Zahnleiter, Diana
AU - Neuhaus, Christine
AU - Lenzner, Steffen
AU - Holz, Frank G
AU - Mangold, Elisabeth
AU - Bolz, Hanno J
AU - Charbel Issa, Peter
PY - 2018/3/19
Y1 - 2018/3/19
N2 - Macular and cone/cone-rod dystrophies (MD/CCRD) demonstrate a broad genetic and phenotypic heterogeneity, with retinal alterations solely or predominantly involving the central retina. Targeted next-generation sequencing (NGS) is an efficient diagnostic tool for identifying mutations in patient with retinitis pigmentosa, which shows similar genetic heterogeneity. To detect the genetic causes of disease in patients with MD/CCRD, we implemented a two-tier procedure consisting of Sanger sequencing and targeted NGS including genes associated with clinically overlapping conditions. Disease-causing mutations were identified in 74% of 251 consecutive MD/CCRD patients (33% of the variants were novel). Mutations in ABCA4, PRPH2 and BEST1 accounted for 57% of disease cases. Further mutations were identified in CDHR1, GUCY2D, PROM1, CRX, GUCA1A, CERKL, MT-TL1, KIF11, RP1L1, MERTK, RDH5, CDH3, C1QTNF5, CRB1, JAG1, DRAM2, POC1B, NPHP1 and RPGR. We provide detailed illustrations of rare phenotypes, including autofluorescence and optical coherence tomography imaging. Targeted NGS also identified six potential novel genotype-phenotype correlations for FAM161A, INPP5E, MERTK, FBLN5, SEMA4A and IMPDH1. Clinical reassessment of genetically unsolved patients revealed subgroups with similar retinal phenotype, indicating a common molecular disease cause in each subgroup.
AB - Macular and cone/cone-rod dystrophies (MD/CCRD) demonstrate a broad genetic and phenotypic heterogeneity, with retinal alterations solely or predominantly involving the central retina. Targeted next-generation sequencing (NGS) is an efficient diagnostic tool for identifying mutations in patient with retinitis pigmentosa, which shows similar genetic heterogeneity. To detect the genetic causes of disease in patients with MD/CCRD, we implemented a two-tier procedure consisting of Sanger sequencing and targeted NGS including genes associated with clinically overlapping conditions. Disease-causing mutations were identified in 74% of 251 consecutive MD/CCRD patients (33% of the variants were novel). Mutations in ABCA4, PRPH2 and BEST1 accounted for 57% of disease cases. Further mutations were identified in CDHR1, GUCY2D, PROM1, CRX, GUCA1A, CERKL, MT-TL1, KIF11, RP1L1, MERTK, RDH5, CDH3, C1QTNF5, CRB1, JAG1, DRAM2, POC1B, NPHP1 and RPGR. We provide detailed illustrations of rare phenotypes, including autofluorescence and optical coherence tomography imaging. Targeted NGS also identified six potential novel genotype-phenotype correlations for FAM161A, INPP5E, MERTK, FBLN5, SEMA4A and IMPDH1. Clinical reassessment of genetically unsolved patients revealed subgroups with similar retinal phenotype, indicating a common molecular disease cause in each subgroup.
KW - Adult
KW - Aged
KW - Cone-Rod Dystrophies/genetics
KW - Cross-Sectional Studies
KW - Eye Proteins/genetics
KW - Female
KW - Genetic Association Studies
KW - Genetic Markers
KW - Humans
KW - Macular Degeneration/genetics
KW - Male
KW - Middle Aged
KW - Mutation
KW - Pedigree
KW - Prognosis
KW - Retrospective Studies
U2 - 10.1038/s41598-018-22096-0
DO - 10.1038/s41598-018-22096-0
M3 - SCORING: Journal article
C2 - 29555955
VL - 8
SP - 4824
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
ER -