446 711

Cited 0 times in

Extremely varied phenotypes in granular corneal dystrophy type 2 heterozygotes.

Authors
 Kyung Eun Han  ;  Seung-il Choi  ;  Woo Suk Chung  ;  Se Hwan Jung  ;  Nicholas Katsanis  ;  Tae-im Kim  ;  Eung Kweon Kim 
Citation
 MOLECULAR VISION, Vol.18 : 1755-1762, 2012 
Journal Title
MOLECULAR VISION
Issue Date
2012
MeSH
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/genetics* ; Case-Control Studies ; Cells, Cultured ; Cornea/metabolism* ; Cornea/pathology ; Corneal Dystrophies, Hereditary/genetics* ; Corneal Dystrophies, Hereditary/metabolism ; Corneal Dystrophies, Hereditary/pathology ; DNA Mutational Analysis ; Extracellular Matrix Proteins/genetics* ; Female ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression ; Genetic Variation ; Heterozygote ; Humans ; Male ; Middle Aged ; Pedigree ; Phenotype ; Severity of Illness Index ; Transforming Growth Factor beta/genetics*
Keywords
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/genetics* ; Case-Control Studies ; Cells, Cultured ; Cornea/metabolism* ; Cornea/pathology ; Corneal Dystrophies, Hereditary/genetics* ; Corneal Dystrophies, Hereditary/metabolism ; Corneal Dystrophies, Hereditary/pathology ; DNA Mutational Analysis ; Extracellular Matrix Proteins/genetics* ; Female ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression ; Genetic Variation ; Heterozygote ; Humans ; Male ; Middle Aged ; Pedigree ; Phenotype ; Severity of Illness Index ; Transforming Growth Factor beta/genetics*
Abstract
PURPOSE: To investigate the phenotypic variability of patients bearing the heterozygous R124H mutation in the TGFBI (transforming growth factor-beta-induced) gene that causes granular corneal dystrophy type 2 (GCD2).

METHODS: We describe the phenotypic range of GCD2 heterozygotes for the common R124H mutation in TGFBI; seven with an extremely mild phenotype and six with an extremely severe phenotype. Detailed slit-lamp photographs of these patients were generated. All patients had no history of ocular surgery and were diagnosed as being heterozygous for GCD2 by DNA analysis from peripheral blood. Expression levels of transforming growth factor-beta-induced protein (TGFBIp) were compared among cultured corneal fibroblasts from ten normal donors.

RESULTS: We report profound differences in the severity of the phenotype across our case series. Two patients with a mild phenotype were diagnosed as unaffected at presentation; however follow-up examinations revealed granular deposits. Importantly, we also observed familial clustering of phenotypic variance; five patients from two families with a mild phenotype showed a similarly mild phenotype within family members. Similarly, six patients from two families with severe phenotypes showed corneal deposits with similar patterns and severity within each distinct family, but distinct patterns between families. TGFBIp expressions from different donor derived cultured corneal fibroblasts were different between one another.

CONCLUSIONS: GCD2 heterozygotes have extremely varied phenotypes between individual patients. However phenotypes were broadly consistent within families, suggesting that the observed variable expressivity might be regulated by other genetic factors that could influence the abundance of TGFBIp or the function of the pathway. From a clinical perspective, our data also highlighted that genetic analysis and meticulous slit-lamp examination in both eyes at multiple time intervals is necessary.
Files in This Item:
T201202703.pdf Download
DOI
22815629
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Kim, Tae-Im(김태임) ORCID logo https://orcid.org/0000-0001-6414-3842
Jung, Se Hwan(정세환)
Choi, Seung Il(최승일) ORCID logo https://orcid.org/0000-0001-7168-8795
Han, Kyung Eun(한경은)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91479
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links