The Clinical Spectrum of Posterior Polymorphous Dystrophy

Cibis, Gerhard W.; Krachmer, Jay A.; Phelps, Charles D.; Weingeist, Thomas A.

doi:10.1001/archopht.1977.04450090051002

Cited by 134 publications

(82 citation statements)

References 11 publications

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“…All other features are common to both conditions and appear to vary in severity. 1,3,4 We believe that a morphological spectrum involving both PPD and ICE may be explained by a 'two-hit hypothesis' similar to that suggested in a case with keratoconus, iris atrophy, and PPD. 6 A first hit would cause 'epithelialization' of the corneal endothelial cells with multilayering and pleomorphism, correlating with the clinical signs of PPD.…”

Section: Commentmentioning

confidence: 60%

Posterior polymorphous dystrophy with polycoria and corectopia

Patel¹,

Loh²,

Morrell³

2004

Eye

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Section: Commentmentioning

confidence: 60%

Posterior polymorphous dystrophy with polycoria and corectopia

Patel¹,

Loh²,

Morrell³

2004

Eye

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“…In family UM:139, the expressivity of the PPCD phenotype varied widely, a characteristic previously described in PPCD families [Cibis et al, 1977]. Typically, the clinical course of PPCD is slowly progressive, and occasionally the clinical course may be severe with corneal decompensation and secondary glaucoma as found for proband, IV-10 [ Moroi et al, 2003].…”

Section: Discussionmentioning

confidence: 84%

“…The clinical phenotype of PPCD can vary from relatively benign Descemet's thickening to severe progression towards vision loss from corneal edema [Cibis et al, 1977;Threlkeld et al, 1994;Weisenthal and Streeten, 1997]. In about 40% of the cases, PPCD includes glaucoma [Bourgeois et al, 1984].…”

Section: Introductionmentioning

confidence: 99%

A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10

Shimizu

Krafchak

Fuse

et al. 2004

American J of Med Genetics Pt A

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Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant disorder characterized by corneal endothelial abnormalities, which can lead to blindness due to loss of corneal transparency and sometimes glaucoma. We mapped a new locus responsible for PPCD in a family in which we excluded the previously reported PPCD locus on 20q11, and the region containing COL8A2 on chromosome 1. Results of a 317-marker genome scan provided significant evidence of linkage of PPCD to markers on chromosome 10, with single-point LOD scores of 2.63, 1.63, and 3.19 for markers D10S208 (at θ = 0.03), D10S1780 (at θ = 0.00), and D10S578 (at θ = 0.06). A maximum multi-point LOD score of 4.35 was found at marker D10S1780. Affected family members shared a haplotype in an 8.55 cM critical interval that was bounded by markers D10S213 and D10S578. Our finding of another PPCD locus, PPCD3, on chromosome 10 indicates that PPCD is genetically heterogeneous. Guttae, a common corneal finding sometimes observed along with PPCD, were found among both affected and unaffected members of the proband's sib ship, but were absent in the younger generations of the family. Evaluation of phenotypic differences between family members sharing the same affected haplotype raises questions about whether differences in disease severity, including differences in response to surgical interventions, could be due to genetic background or other factors independent of the PPCD3 locus.

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“…A diagnosis of PPCD was based on established clinical criteria documented previously in detail. 1,16 For inclusion in this analysis, the presence of ZEB1 coding and/or splice-site mutations by direct sequencing had previously been excluded. 11,16,17 All probands identified to be positive for ZEB1 locus deletions in the current study were also negative for mutations in COL8A2, either by Sanger sequencing or by whole-exome sequencing (WES) (unpublished data).…”

Section: Study Subjects and Clinical Examinationmentioning

confidence: 99%

“…Corneal endothelial cell dysfunction can lead to corneal oedema, secondary glaucoma, and loss of vision. 1 Endothelial cells from affected corneas demonstrate characteristics of epithelial cells including the ability to proliferate, leading to focal formation of multilayered areas, and multilamination of Descemet membrane. [2][3][4] PPCD is genetically heterogeneous with three identified loci; PPCD1 (OMIM #122000) on chromosome 20p with a currently undefined causative gene, [5][6][7] PPCD2 (OMIM #609140) associated with mutations in COL8A2, 8 and PPCD3 (OMIM #609141) caused by mutations in ZEB1.…”

Section: Introductionmentioning

confidence: 99%

Heterozygous deletions at the ZEB1 locus verify haploinsufficiency as the mechanism of disease for posterior polymorphous corneal dystrophy type 3

Lišková

Evans²,

Davidson³

et al. 2015

Eur J Hum Genet

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A substantial proportion of patients with posterior polymorphous corneal dystrophy (PPCD) lack a molecular diagnosis. We evaluated 14 unrelated probands who had a clinical diagnosis of PPCD who were previously determined to be negative for mutations in ZEB1 by direct sequencing. A combination of techniques was used including whole-exome sequencing (WES), single-nucleotide polymorphism (SNP) array copy number variation (CNV) analysis, quantitative real-time PCR, and long-range PCR. Segregation of potentially pathogenic changes with disease was confirmed, where possible, in family members. A putative run of homozygosity on chromosome 10 was identified by WES in a three-generation PPCD family, suggestive of a heterozygous deletion. SNP array genotyping followed by long-range PCR and direct sequencing to define the breakpoints confirmed the presence of a large deletion that encompassed multiple genes, including ZEB1. Identification of a heterozygous deletion spanning ZEB1 prompted us to further investigate potential CNVs at this locus in the remaining probands, leading to detection of two additional heterozygous ZEB1 gene deletions. This study demonstrates that ZEB1 mutations account for a larger proportion of PPCD than previously estimated, and supports the hypothesis that haploinsufficiency of ZEB1 is the underlying molecular mechanism of disease for PPCD3.

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The Clinical Spectrum of Posterior Polymorphous Dystrophy

Cited by 134 publications

References 11 publications

Posterior polymorphous dystrophy with polycoria and corectopia

Posterior polymorphous dystrophy with polycoria and corectopia

A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10

Heterozygous deletions at the ZEB1 locus verify haploinsufficiency as the mechanism of disease for posterior polymorphous corneal dystrophy type 3

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