Universität zu Köln

Duvvari, Maheswara R., van de Ven, Johannes P. H., Geerlings, Maartje J., Saksens, Nicole T. M., Bakker, Bjorn, Henkes, Arjen, Neveling, Kornelia, del Rosario, Marisol, Westra, Dineke, van den Heuvel, Lambertus P. W. J., Schick, Tina, Fauser, Sascha, Boon, Camiel J. F., Hoyng, Carel B., de Jong, Eiko K. and den Hollander, Anneke I. (2016). Whole Exome Sequencing in Patients with the Cuticular Drusen Subtype of Age-Related Macular Degeneration. PLoS One, 11 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people worldwide. Cuticular drusen (CD) is a clinical subtype of AMD, which typically displays an earlier age at onset, and has a strong genetic component. Genetic studies support a role for rare sequence variants in CD susceptibility, and rare sequence variants in the CFH gene have been identified in 8.8% of CD cases. To further explore the role of rare variants in CD, we performed whole exome sequencing (WES) in 14 affected members of six families and 12 sporadic cases with CD. We detected rare sequence variants in CFH and FBLN5, which previously were shown to harbor rare variants in patients with CD. In addition, we detected heterozygous rare sequence variants in several genes encoding components of the extracellular matrix (ECM), including FBLN1, FBLN3/EFEMP1, FBLN5, FBLN6/HMCN1, FBN2, and COL15A1. Two rare pathogenic variants were identified in the COL15A1 gene: one in a sporadic case and another was found to segregate in a family with six affected individuals with CD. In addition, two rare pathogenic variants were identified in the FGL1 gene in three unrelated CD cases. These findings suggest that alterations in the ECM and in the coagulation pathway may play a role in the pathogenesis of CD. The identified candidate genes require further analyses in larger cohorts to confirm their role in the CD subtype of AMD. No evidence was found of rare sequence variants in a single gene that segregate with CD in the six families, suggesting that the disease is genetically heterogeneous.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Duvvari, Maheswara R. UNSPECIFIED UNSPECIFIED UNSPECIFIED van de Ven, Johannes P. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Geerlings, Maartje J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saksens, Nicole T. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bakker, Bjorn UNSPECIFIED UNSPECIFIED UNSPECIFIED Henkes, Arjen UNSPECIFIED UNSPECIFIED UNSPECIFIED Neveling, Kornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED del Rosario, Marisol UNSPECIFIED UNSPECIFIED UNSPECIFIED Westra, Dineke UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Heuvel, Lambertus P. W. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schick, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Boon, Camiel J. F. 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:38-281049
DOI:	10.1371/journal.pone.0152047
Journal or Publication Title:	PLoS One
Volume:	11
Number:	3
Date:	2016
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BASAL LAMINAR DRUSEN; EXTRACELLULAR-MATRIX; BRUCHS MEMBRANE; GRADING SYSTEM; HIGH-RISK; CFH GENE; DISEASE; MUTATION; RARE; CLASSIFICATION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28104