Document Detail

Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucoma.
MedLine Citation:
PMID:  23621901     Owner:  NLM     Status:  MEDLINE    
Primary open angle glaucoma (POAG) is a genetically and phenotypically complex disease that is a leading cause of blindness worldwide. Previously we completed a genome-wide scan for early-onset POAG that identified a locus on 9q22 (GLC1J). To identify potential causative variants underlying GLC1J, we used targeted DNA capture followed by high throughput sequencing of individuals from four GLC1J pedigrees, followed by Sanger sequencing to screen candidate variants in additional pedigrees. A mutation likely to cause early-onset glaucoma was not identified, however COL15A1 variants were found in the youngest affected members of 7 of 15 pedigrees with variable disease onset. In addition, the most common COL15A1 variant, R163H, influenced the age of onset in adult POAG cases. RNA in situ hybridization of mouse eyes shows that Col15a1 is expressed in the multiple ocular structures including ciliary body, astrocytes of the optic nerve and cells in the ganglion cell layer. Sanger sequencing of COL18A1, a related multiplexin collagen, identified a rare variant, A1381T, in members of three additional pedigrees with early-onset disease. These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG.
J L Wiggs; G R Howell; K Linkroum; W Abdrabou; E Hodges; C E Braine; L R Pasquale; G J Hannon; J L Haines; S W M John
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-05-27
Journal Detail:
Title:  Clinical genetics     Volume:  84     ISSN:  1399-0004     ISO Abbreviation:  Clin. Genet.     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-07-10     Completed Date:  2014-02-21     Revised Date:  2014-08-04    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  167-74     Citation Subset:  IM    
Copyright Information:
© 2013 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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MeSH Terms
Age of Onset
Collagen / genetics*
Collagen Type XVIII / genetics*
Genetic Variation*
Glaucoma, Open-Angle / genetics*
Middle Aged
Polymorphism, Single Nucleotide
Grant Support
EY00947/EY/NEI NIH HHS; EY010886/EY/NEI NIH HHS; EY011721/EY/NEI NIH HHS; EY015872/EY/NEI NIH HHS; EY021525/EY/NEI NIH HHS; P30 EY014104/EY/NEI NIH HHS; P30 EY014104/EY/NEI NIH HHS; R01 EY009847/EY/NEI NIH HHS; R01 EY010886/EY/NEI NIH HHS; R01 EY015872/EY/NEI NIH HHS; R01 EY022305/EY/NEI NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/COL15A1 protein, human; 0/Collagen Type XVIII; 9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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