Document Detail


Replication and refinement of linkage of posterior polymorphous corneal dystrophy to the posterior polymorphous corneal dystrophy 1 locus on chromosome 20.
MedLine Citation:
PMID:  17438387     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The study purpose was to identify the genetic basis of posterior polymorphous corneal dystrophy, an autosomal dominant disorder of the corneal endothelium that is associated with the development of corneal edema, necessitating corneal transplantation for visual rehabilitation. Glaucoma also develops in up to 40% of patients with posterior polymorphous corneal dystrophy. METHODS: Linkage analysis, using microsatellite markers previously used to demonstrate linkage of posterior polymorphous corneal dystrophy to the chromosome 20 candidate region known as posterior polymorphous corneal dystrophy 1, was performed in 29 members of a family with posterior polymorphous corneal dystrophy. Thirty-four microsatellite markers were used to refine the posterior polymorphous corneal dystrophy 1 interval. TCF8, located on chromosome 10, was screened in an affected family member to exclude posterior polymorphous corneal dystrophy 3. RESULTS: Significant evidence of linkage to the posterior polymorphous corneal dystrophy 1 interval was obtained with both single-point and multipoint analyses. The largest single-point log odds ratio score obtained was 4.38 (theta=0) at marker D20S471; within 4.7 Mbp (7.2 cM) of D20S471 eight markers provided single-point log odds ratio scores of greater than 3.00 and three markers provided single-point log odds ratio scores greater than 4.00. The largest multipoint log odds ratio score obtained was 4.83, found across the adjacent markers D20S844, D20S191, D20S484, and D20S111. The support interval for posterior polymorphous corneal dystrophy 1 in the family we report is approximately 13.5 Mbp (10 cM) long and lies between the markers D20S182 and D20S195. Eleven markers have multipoint log odds ratio scores greater than 4.0 within this region. No coding region mutations were identified in TCF8 in an affected member of the family, effectively excluding posterior polymorphous corneal dystrophy 3. CONCLUSIONS: The originally described 19.8 cM posterior polymorphous corneal dystrophy 1 candidate disease interval has been refined to a 10 cM interval between markers D20S182 and D20S195. A portion of this refined interval overlaps a more recently reported posterior polymorphous corneal dystrophy 1 interval, with only 20 known and predicted genes mapped to the 2.4 cM common interval.
Authors:
Vivek S Yellore; Jeanette C Papp; Eric Sobel; M Ali Khan; Sylvia A Rayner; Debora B Farber; Anthony J Aldave
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genetics in medicine : official journal of the American College of Medical Genetics     Volume:  9     ISSN:  1098-3600     ISO Abbreviation:  Genet. Med.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-17     Completed Date:  2007-07-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9815831     Medline TA:  Genet Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  228-34     Citation Subset:  IM    
Affiliation:
Cornea Service, The Jules Stein Eye Institute, Department of Human Genetics, and Retinal Biochemistry Laboratory, David Geffen School of Medicine at University of California Los Angeles, California 90095, USA.
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MeSH Terms
Descriptor/Qualifier:
Chromosome Mapping
Chromosomes, Human, Pair 20*
Corneal Dystrophies, Hereditary / epidemiology,  genetics*,  pathology
Endothelium, Corneal / pathology
Genetic Testing
Homeodomain Proteins / genetics,  metabolism
Humans
Linkage (Genetics)*
Lod Score
Pedigree
Transcription Factors / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
K08 EY016079/EY/NEI NIH HHS; R01 EY008285/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/Transcription Factors; 0/ZEB1 protein, human

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


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