Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004 Nov 1;130A(4):372-7.
doi: 10.1002/ajmg.a.30267.

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

Satoko Shimizu  1 , Charles Krafchak, Nobuo Fuse, Michael P Epstein, Miriam T Schteingart, Alan Sugar, Maya Eibschitz-Tsimhoni, Catherine A Downs, Frank Rozsa, Edward H Trager, David M Reed, Michael Boehnke, Sayoko E Moroi, Julia E Richards
Affiliations

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

Satoko Shimizu et al. Am J Med Genet A. .

Abstract

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 (circumflex)theta = 0.03), D10S1780 (at (circumflex)theta = 0.00), and D10S578 (at (circumflex)theta = 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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Family UM:139 with PPCD. Among those individuals for whom molecular data were generated for use in the analysis (marked with +), filled symbols are individuals with PPCD, open symbols are individuals deemed unaffected with PPCD, and a cross within symbol indicates individuals who were scored as having an indeterminate PPCD status for purposes of analysis. Open symbols not marked with + are individuals for whom molecular data were not generated; they are free of PPCD by family report, but were not examined by us. Arrow indicates proband. Squares represent males; circles represent females. Diagonal line through symbol indicates individual is deceased. Box to the left of the + indicates presence (black dot) or absence (gray box) of guttae. Data on guttae are not available for individuals not marked with a box. Other significant eye disease in the family includes: angle-closure glaucoma in the proband (IV-10); primary open-angle glaucoma (POAG) in III-11; blindness from an accident in I-1; blindness from unspecified glaucoma in II-5; and blindness from cataract surgery in III-1. Haplotypes are displayed for each individual genotyped, with a genetic inclusion interval between D10S213 and D10S578 indicated by recombination events apparent in data for individuals V-2 and VI-1. A recombination event in individual V-18 is not considered to further reduce the interval since this individual is unaffected in a family showing evidence of reduced penetrance.
Fig. 2
Fig. 2
Multipoint analysis of markers on 10p provides strong evidence of linkage with a maximum multipoint LOD score of 4.35 at marker D10S1780 when data from the whole family were used (solid line), and 3.53 at marker D10S208 when an affecteds-only analysis was done (dotted line). The map position indicates the distance from the tip of the short arm of the chromosome to the position of the marker tested. The LOD score indicates the level of statistical significance associated with the finding of possible linkage for each of the loci tested along the chromosome.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Albin RL. Fuch’s corneal dystrophy in a patient with mitochondrial DNA mutations. J Med Genet. 1988;35:258–259. - PMC - PubMed
    1. Alport AC. Hereditary familial congenital haemorrhagic nephritis. Brit Med J. 1927;1:504–506. - PMC - PubMed
    1. Biswas S, Munier FL, Yardley J, Hart-Holden N, Perveen R, Cousin P, Sutphin JE, Noble B, Batterbury M, Kielty C, Hackett A, Bonshek R, Ridgway A, McLeod D, Sheffield VC, Stone EM, Schorderet DF, Black GCM. Missense mutations in COL8A2, the gene encoding the alpha-2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy. Hum Mol Genet. 2001;10:2415–2423. - PubMed
    1. Boehnke M. Allele frequency estimation from data on relatives. Am J Hum Genet. 1991;48:22–25. - PMC - PubMed
    1. Bourgeois J, Shields MB, Thresher R. Open-angle glaucoma associated with posterior polymorphous dystrophy. A clinicopathologic study. Ophthalmol. 1984;91:420–423. - PubMed

Publication types

Substances

LinkOut - more resources