Universität zu Köln

Duvvari, Maheswara R., Saksens, Nicole T. M., van de Ven, Johannes P. H., de Jong-Hesse, Yvonne, Schick, Tina, Nillesen, Willy M., Fauser, Sascha, Hoefsloot, Lies H., Hoyng, Carel B., de Jong, Eiko K. and den Hollander, Anneke I. (2015). Analysis of rare variants in the CFH gene in patients with the cuticular drusen subtype of age-related macular degeneration. Mol. Vis., 21. S. 285 - 293. ATLANTA: MOLECULAR VISION. ISSN 1090-0535

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Abstract

Purpose: Age-related macular degeneration (AMD) and cuticular drusen (CD), a clinical subtype of AMD, have been linked to genetic variants in the complement factor H (CFH) gene. In this study, we aimed to investigate the frequency of rare variants in the CFH gene in 180 cases with CD. In addition, we aimed to determine the frequency of a previously reported rare, highly penetrant CFH variant (p. Arg1210Cys) in a Dutch-German non-CD-type AMD case-control cohort, and to describe the phenotype of patients carrying the p. Arg1210Cys variant. Methods: Study subjects were selected from the European Genetic Database (EUGENDA), a joint AMD database of the Radboud University Medical Centre and the University Hospital of Cologne, and graded at the Cologne Image Reading Centre and Laboratory (CIRCL). Additionally, two CD cases were recruited from the VU Medical Centre in Amsterdam. The CFH gene was analyzed in 180 CD cases with Sanger sequencing. All identified variants were analyzed for potential damaging effects with prediction software tools Sorting Intolerant from Tolerant (SIFT) and Polymorphism Phenotyping (PolyPhen). In addition, we genotyped the p. Arg1210Cys variant in 813 non-CD type AMD cases and 1175 controls. Results: Sequencing identified 11 rare, heterozygous missense variants, one frameshift variant, and one splice acceptor site variant in 16 CD cases. The p. Arg1210Cys variant was identified in two CD cases but was not identified in our Dutch-German non-CD-type AMD case-control cohort. Conclusions: The present study identified the presence of rare variants in the CFH gene in 16 (8.8%) of 180 patients with the CD subtype of AMD. The carriers of rare CFH variants displayed a significantly earlier age at onset than non-carriers (p=0.016). The rare missense variant p. Arg1210Cys was identified in two CD cases, but was not detected in 813 non-CD type AMD cases or in the 1,175 controls of our Dutch-German cohort. The current study suggests that the p. Arg1210Cys variant may be restricted to a subset of patients with the CD subtype of AMD. Detailed clinical pheno-typing, including fluorescein angiography, of patients with AMD carrying the p. Arg1210Cys variant in other cohorts is required to confirm this finding.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Duvvari, Maheswara R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saksens, Nicole T. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED van de Ven, Johannes P. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Jong-Hesse, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Schick, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Nillesen, Willy M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoefsloot, Lies H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Jong, Eiko K. UNSPECIFIED UNSPECIFIED UNSPECIFIED den Hollander, Anneke I. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-409807
Journal or Publication Title:	Mol. Vis.
Volume:	21
Page Range:	S. 285 - 293
Date:	2015
Publisher:	MOLECULAR VISION
Place of Publication:	ATLANTA
ISSN:	1090-0535
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEMOLYTIC-UREMIC SYNDROME; FACTOR-H MUTATIONS; HIGH-RISK; DISEASE; BINDING; ASSOCIATION; HEPARIN; CELLS; C3B Multiple languages Biochemistry & Molecular Biology; Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40980