Universität zu Köln

Birtel, Johannes, Eisenberger, Tobias, Gliem, Martin, Mueller, Philipp L., Herrmann, Philipp, Betz, Christian, Zahnleiter, Diana, Neuhaus, Christine, Lenzner, Steffen, Holz, Frank G., Mangold, Elisabeth, Bolz, Hanno J. and Issa, Peter Charbel ORCID: 0000-0002-0351-6673 (2018). Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Birtel, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Eisenberger, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Gliem, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Philipp L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herrmann, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Betz, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Zahnleiter, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Neuhaus, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Lenzner, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Holz, Frank G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mangold, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolz, Hanno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Issa, Peter Charbel UNSPECIFIED orcid.org/0000-0002-0351-6673 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-192599
DOI:	10.1038/s41598-018-22096-0
Journal or Publication Title:	Sci Rep
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LINKED RETINITIS-PIGMENTOSA; LEBER CONGENITAL AMAUROSIS; INHERITED RETINAL DISEASE; AUTOSOMAL-RECESSIVE CONE; ALAGILLE-SYNDROME; KIF11 MUTATIONS; MOLECULAR DIAGNOSIS; NONSENSE MUTATION; JOUBERT-SYNDROME; RPGR Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19259