Changing Indications for Penetrating Keratoplasty, 1984–1988

Mohamadi, Parivash; McDonnell, Jan M.; Irvine, John A.; McDonnell, Peter J.; Rao, Narsing A.; Smith, Ronald E.

doi:10.1016/0002-9394(89)90506-0

Cited by 49 publications

(17 citation statements)

References 5 publications

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“…People with this disease are currently the most frequent recipients of corneal transplants. 5 FECD generally begins in the fifth decade of life and can progress slowly over the next two to three decades. 6,7 Although rare, there is also an early onset form of this disease.…”

Section: Introductionmentioning

confidence: 99%

Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients

Mok

Kim

Joo

2008

Eye

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Purpose To investigate the possibility of collagen type VIII a2 (COL8A2) as a potential susceptibility gene for Korean patients with Fuchs' corneal dystrophy (FECD), we performed mutation screening of the COL8A2 gene. Methods A total of 25 FECD patients were screened, including 15 patients from six pedigrees with early onset FECD and an additional 10 unrelated patients, all of Korean ancestry. Seventy-three control individuals without corneal disease were selected from the general population. PCRFSSCP and direct sequencing were used to screen genetic variations in COL8A2. The pathogenic impact of these sequence variants was evaluated through the SIFT and PolyPhen algorithms.Results We have identified a novel heterozygous mutation, Q455V, in exon 2 of COL8A2. All patients of Korean pedigrees with FECD had the Q455V mutation, and two out of nine unrelated cases also had this mutation. But it was not present in unaffected individuals from these pedigrees or from control groups. Two heterozygous missense mutations, R155Q and T502M, were also observed, but, they showed no significant difference between FECD patients and controls. The allele frequencies of A35A and G495G, which were synonymous substitutions, were significantly associated with FECD. Both Q455V and T502M were predicted as deleterious mutations by computational methods using PolyPhen and SIFT. Conclusions Our data constitute the first report of a heterozygous Q455V mutation of the COL8A2 gene in Korean patients with FECD. Q455V may be the causative defect in the development and progression of Korean FECD patients.

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Section: Introductionmentioning

confidence: 99%

Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients

Mok

Kim

Joo

2008

Eye

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“…Epidemiological data regarding its incidence or prevalence are unavailable. An indirect measure of the impact of the disease comes from surveys of clinical indications for corneal transplantation which rank FECD as one of the commonest indications for corneal transplantation (up to 19%) performed in developed countries (6)(7)(8)(9)(10). The high prevalence of this dystrophy co-existing with cataract in an older age group means that it is a risk factor for the requirement for penetrating keratoplasty (PK) subsequent to cataract surgery.…”

Section: Introductionmentioning

confidence: 99%

Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy

Biswas

Munier²,

Yardley³

et al. 2001

Human Molecular Genetics

345

304

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“…Visual disability from this disease is currently the major reason for corneal transplantation. 1 The initial stages of FCD typically begin in the fifth through seventh decades of life and are characterized by localized thickening of Descemet's membrane and the development of nodular excrescences called guttae. This early phase is followed by long-term decreases in the density and ion transport functions of the overlying corneal endothelial cells, which allows excess water to accumulate in the cornea.…”

mentioning

confidence: 99%

Inheritance of a NovelCOL8A2Mutation Defines a Distinct Early-Onset Subtype of Fuchs Corneal Dystrophy

Gottsch

Sundin

Liu³

et al. 2005

Invest. Ophthalmol. Vis. Sci.

191

174

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PURPOSE.To characterize the genetic basis and phenotype of inherited Fuchs corneal dystrophy (FCD). METHODS.DNA from blood was used for genome-wide linkage scans with tandem repeat polymorphisms. Mutation detection involved sequencing PCR-amplified exons. Families with FCD were clinically evaluated and graded on the Krachmer severity scale. Confocal specular microscopy visualized the morphology of endothelial guttae, small protrusions of Descemet's membrane that are characteristic of FCD. RESULTS.Linkage was obtained to 1p34.3-p32 for the autosomal dominant kindred originally reported by Magovern in 1979. All 21 cases with FCD and one with posterior polymorphous dystrophy were heterozygous for L450W, a novel point mutation in the COL8A2 gene. Of 62 independent cases of familial FCD, none had the previously reported mutations in COL8A2. Corneal guttae in COL8A2 patients were small, rounded, and associated with the endothelial cell center. This contrasts with common FCD, in which guttae were larger, sharply peaked, and initially positioned at edges of endothelial cells. The profile of age and disease severity for the L450W FCD kindred suggested that disease onset occurred in infancy, compared with an average age of onset of 50 years estimated for 201 familial FCD patients in 62 other families. CONCLUSIONS.A novel pathogenic L450W COL8A2 mutation was identified and its highly distinctive pathology characterized. This indicates that COL8A2 mutations give rise to a rare subtype of FCD. This study also provides the first direct evidence that COL8A2-FCD progresses from early to late stages in 25 years, a rate similar to that estimated for late-onset FCD. (Invest Ophthalmol Vis Sci. 2005;46:1934 -1939) DOI: 10.1167/iovs.04-0937 F uchs corneal dystrophy (FCD) is a primary disorder of the endothelium that leads to progressive edema of the corneal stroma (OMIM 136800; Online Mendelian Inheritance in Man; http://www.ncbi.nlm.nih.gov/Omim/ provided in the public domain by the National Center for Biotechnology Information, Bethesda, MD). Visual disability from this disease is currently the major reason for corneal transplantation.1 The initial stages of FCD typically begin in the fifth through seventh decades of life and are characterized by localized thickening of Descemet's membrane and the development of nodular excrescences called guttae. This early phase is followed by long-term decreases in the density and ion transport functions of the overlying corneal endothelial cells, which allows excess water to accumulate in the cornea.2-8 Several reports, including the original description by Fuchs, have indicated that two to three times as many females as males are affected by the disease. 2,7,9 As many as 50% of clinical cases of FCD may show familial clustering, 9 and the disease generally follows an autosomal dominant pattern of inheritance. 10 -15 Nearly all these families show inheritance of late-onset FCD, whereas rare cases 12,14 show disease onset as early as the first decade, with extensive corneal edema by the third ...

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Changing Indications for Penetrating Keratoplasty, 1984–1988

Cited by 49 publications

References 5 publications

Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients

Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients

Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy

Inheritance of a NovelCOL8A2Mutation Defines a Distinct Early-Onset Subtype of Fuchs Corneal Dystrophy

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