No pathogenic mutations identified in the COL8A1 and COL8A2 genes in familial Fuchs corneal dystrophy.
OBJECTIVE
To investigate the genetic basis of late-onset, familial Fuchs endothelial corneal dystrophy (FECD) through screening of the COL8A1 and COL8A2 genes, in which mutations have been associated with both early and late-onset, familial and sporadic FECD.


METHODS
DNA extraction, PCR amplification, and direct sequencing of the COL8A1 and COL8A2 genes was performed in affected and unaffected members of 15 unrelated families with two or more members with late-onset FECD.


RESULTS
Screening of the COL8A1 gene did not reveal sequence variants in any affected individuals from the 15 FECD families. In the COL8A2 gene, the previously identified mutations presumed to play a pathogenic role in cases of familial FECD (Arg155Gln, Leu450Trp, and Gln455Lys) were not discovered in any of the affected patients. A mutation previously considered causative of FECD (Arg434His) was shown not to segregate with the disease in the one family in which it was identified. Two previously identified single-nucleotide polymorphisms (SNPs), Pro575Leu and Pro586Pro, were identified in a single affected individual and three affected individuals (two families), respectively.


CONCLUSIONS
The Arg434His mutation in the COL8A2 gene, previously associated with FECD, has been shown not to segregate with the disease phenotype, and thus may not be considered a disease-causing mutation. The absence of pathogenic mutations identified in the COL8A1 or COL8A2 genes in affected members of 15 pedigrees with familial FECD indicates that other genetic factors are involved in the development of this autosomal dominant corneal dystrophy.
Aldave
Anthony J
AJ
Cornea Service, Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, California 90095, USA. aldave@jsei.ucla.edu
Rayner
Sylvia A
SA
Salem
Andrew K
AK
Yoo
Gina L
GL
Kim
Brian T
BT
Saeedian
Monika
M
Sonmez
Baris
B
Yellore
Vivek S
VS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024102:Collagen Type VIII / Q000235:genetics*; D004247:DNA / Q000302:isolation & purification; D004252:DNA Mutational Analysis; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
C443712:COL8A2 protein, human; D024102:Collagen Type VIII; D004247:DNA