Candidate gene screening for posterior polymorphous dystrophy.
OBJECTIVE
To perform candidate gene screening for posterior polymorphous corneal dystrophy (PPCD). The initial 3 genes chosen, ID1, BCL2L1, and VSX1, lie within the region on chromosome 20 to which the PPCD gene has been linked, and mutations in VSX1 have previously been identified in patients with PPCD.


METHODS
DNA extraction, PCR amplification, and direct sequencing of the VSX1, BCL2L1, and ID1 genes were performed in 14 affected patients (12 families) as well as in unaffected family members and healthy control subjects.


RESULTS
No coding region mutations in the BCL2L1 or ID1 genes were identified in affected patients. In the VSX1 gene, the previously identified Gly160Asp missense change was not present in any of our 12 probands, and the Asp144Glu mutation was identified in 1 affected patient as well as 1 unaffected control individual. Additionally, 2 synonymous substitutions were identified, Ala182Ala (8 affected patients from 8 families) and Gly239Gly (1 affected patient and 1 unaffected patient from the same family). In the ID1 gene, the synonymous substitution Gly216Gly was observed in 2 affected patients (2 families) who also demonstrated a single nucleotide change in both the 5'UTR (2129T>C) and 3'UTR (3267A>G). Another 5'UTR change, 2177T>C, was identified in 1 affected patient and his unaffected parent, both of whom also demonstrated the 2129T>C and 3267A>G changes.


CONCLUSIONS
None of the 12 probands with PPCD demonstrated the previously described Gly160Asp mutation within the VSX1 gene. The Asp144Glu missense change, present in an affected patient as well as an unaffected control individual, appears to be a rare polymorphism, not a disease-causing mutation. No coding region changes were identified in the ID1 or BCL2L1 genes. Therefore, although we report a number of novel polymorphisms in the VSX1 and ID1 genes, the failure to identify any sequence variants that sort with the disease phenotype suggests that other genetic factors are involved in PPCD.
Aldave
Anthony J
AJ
Cornea Service, The Jules Stein Eye Institute, University of California, Los Angeles, California 90095, USA. aldave@jsei.ucla.edu
Yellore
Vivek S
VS
Principe
Alexandre H
AH
Abedi
Gelareh
G
Merrill
Kevin
K
Chalukya
Meenal
M
Small
Kent W
KW
Udar
Nitin
N
D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D005136:Eye Proteins; D018398:Homeodomain Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D014157:Transcription Factors; C491583:VSX1 protein, human; D051020:bcl-X Protein