No pathogenic mutations identified in the COL8A2 gene or four positional candidate genes in patients with posterior polymorphous corneal dystrophy.
OBJECTIVE
To identify the genetic basis of posterior polymorphous corneal dystrophy (PPCD) through screening of four positional candidate genes and the COL8A2 gene, in which a presumed pathogenic mutation has previously been identified in affected patients.


METHODS
DNA extraction, PCR amplification, and direct sequencing of the COL8A2, BFSP1, CST3, MMP9, and SLPI genes were performed in 14 unrelated, affected patients and in unaffected family members.


RESULTS
In the COL8A2 gene, the previously identified, presumed pathogenic mutation (Gln455Lys) was not discovered in any of the affected patients. A missense mutation, Thr502Met, was identified in 2 of the 14 affected probands, although it was not considered to be pathogenic, as it has been identified in unaffected individuals. Although several novel and previously identified single nucleotide polymorphisms producing synonymous and missense amino acid substitutions were identified in the COL8A2, BFSP1, CST3, MMP9, and SLPI genes, no presumed pathogenic sequence variants were found.


CONCLUSIONS
No pathogenic mutations were identified in the COL8A2 gene or in several positional candidate genes in a series of patients with PPCD, indicating that other genetic factors are involved in the development of this autosomal dominant corneal dystrophy.
Yellore
Vivek S
VS
Jules Stein Eye Institute, University of California-Los Angeles, 100 Stein Plaza, Los Angeles, CA 90095, USA.
Rayner
Sylvia A
SA
Emmert-Buck
Leslie
L
Tabin
Geoffrey C
GC
Raber
Irving
I
Hannush
Sadeer B
SB
Stulting
R Doyle
RD
Sampat
Kapil
K
Momi
Rominder
R
Principe
Alexandre H
AH
Aldave
Anthony J
AJ
D024102:Collagen Type VIII / Q000235:genetics*; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics*; D053481:Secretory Leukocyte Peptidase Inhibitor; D017422:Sequence Analysis, DNA
C443712:COL8A2 protein, human; C525030:CST3 protein, human; D024102:Collagen Type VIII; D055316:Cystatin C; D015891:Cystatins; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; C079098:filensin; D020780:Matrix Metalloproteinase 9