title: A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10.
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.
authors.affiliation: Department of Ophthalmology & Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.
authors.forename: Satoko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Charles
authors.initials: C
authors.lastname: Krafchak
authors.forename: Nobuo
authors.initials: N
authors.lastname: Fuse
authors.forename: Michael P
authors.initials: MP
authors.lastname: Epstein
authors.forename: Miriam T
authors.initials: MT
authors.lastname: Schteingart
authors.forename: Alan
authors.initials: A
authors.lastname: Sugar
authors.forename: Maya
authors.initials: M
authors.lastname: Eibschitz-Tsimhoni
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Downs
authors.forename: Frank
authors.initials: F
authors.lastname: Rozsa
authors.forename: Edward H
authors.initials: EH
authors.lastname: Trager
authors.forename: David M
authors.initials: DM
authors.lastname: Reed
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.forename: Sayoko E
authors.initials: SE
authors.lastname: Moroi
authors.forename: Julia E
authors.initials: JE
authors.lastname: Richards
mesh_terms: D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D040641:Quantitative Trait Loci
chemical_list: D005819:Genetic Markers