Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy

被引:160
|
作者
Birtel, Johannes [1 ,2 ]
Eisenberger, Tobias [3 ]
Gliem, Martin [1 ,2 ]
Mueller, Philipp L. [1 ,2 ]
Herrmann, Philipp [1 ,2 ]
Betz, Christian [3 ]
Zahnleiter, Diana [3 ]
Neuhaus, Christine [3 ]
Lenzner, Steffen [3 ]
Holz, Frank G. [1 ,2 ]
Mangold, Elisabeth [4 ]
Bolz, Hanno J. [3 ,5 ]
Issa, Peter Charbel [1 ,2 ,6 ,7 ]
机构
[1] Univ Bonn, Dept Ophthalmol, Bonn, Germany
[2] Univ Bonn, Ctr Rare Dis Bonn ZSEB, Bonn, Germany
[3] Bioscientia Ctr Human Genet, Ingelheim, Germany
[4] Univ Bonn, Inst Human Genet, Bonn, Germany
[5] Univ Hosp Cologne, Inst Human Genet, Cologne, Germany
[6] Oxford Univ Hosp NHS Fdn Trust, Oxford Eye Hosp, Oxford, England
[7] Univ Oxford, Nuffield Lab Ophthalmol, Dept Clin Neurosci, Oxford, England
来源
SCIENTIFIC REPORTS | 2018年 / 8卷
关键词
RECESSIVE RETINITIS-PIGMENTOSA; RETINAL DYSTROPHY; MOLECULAR DIAGNOSIS; NONSENSE MUTATION; CONE; RPGR; SPECTRUM; CRB1; IDENTIFICATION; LYMPHEDEMA;
D O I
10.1038/s41598-018-22096-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:11
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