Analysis of fifteen positional candidate genes for Schnyder crystalline corneal dystrophy.
OBJECTIVE
To identify the genetic basis of Schnyder crystalline corneal dystrophy (SCCD) through screening of positional candidate genes in affected patients.


METHODS
Mutation screening of fifteen genes (CORT, CLSTN1, CTNNBIP1, DFFA, ENO1, GPR157, H6PD, KIF1B, LOC440559, LZIC, MGC4399, PEX14, PGD, PIK3CD, and SSB1) that lie within the candidate gene region for SCCD was performed in members of two families affected with SCCD.


RESULTS
No presumed disease-causing mutations were identified in affected patients. Seventeen previously described single nucleotide polymorphisms (SNPs) were identified in eight of the candidate genes. Novel SNPs were identified in both affected and unaffected individuals in GPR157 (c.795C>T [Arg218Leu]; c.811C>T [Ala223Val]), MGC4399 (c.1024G>C [Leu277Leu]), and H6PD (c.754A>C [Asp151Ala]).


CONCLUSIONS
No pathogenic mutations were identified in fifteen positional candidate genes in two families with SCCD. As the candidate gene region in each SCCD family previously examined with haplotype analysis has been mapped to the same chromosomal region, the absence of pathogenic mutations in these positional candidates in the families we examined reduces the number of remaining positional candidate genes by half, and the number of remaining candidate genes with a known gene function by two-thirds. We anticipate that screening of the remaining positional candidate genes will lead to the identification of the genetic basis of SCCD.
Aldave
Anthony J
AJ
Cornea Service, Jules Stein Eye Institute, University of California, Los Angeles, CA, USA. aldave@jsei.ucla.edu
Rayner
Sylvia A
SA
Principe
Alexandre H
AH
Affeldt
John A
JA
Katsev
Douglas
D
Yellore
Vivek S
VS
D000293:Adolescent; D000328:Adult; D002648:Child; D002784:Cholesterol / Q000378:metabolism; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000378:metabolism; D003318:Corneal Opacity / Q000235:genetics / Q000378:metabolism; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D015745:Granuloma, Foreign-Body / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
D005136:Eye Proteins; D005819:Genetic Markers; D002784:Cholesterol