Analysis of COL8A2 gene mutation in Japanese patients with Fuchs' endothelial dystrophy and posterior polymorphous dystrophy.
OBJECTIVE
To determine whether Japanese patients with Fuchs' endothelial corneal dystrophy (FECD) and posterior polymorphous dystrophy (PPMD) carry mutations in the COL8A2 gene, and to investigate the possible pathogenicity of the COL8A2 gene in these corneal dystrophies.


METHODS
DNA analysis of the COL8A2 gene was performed in 15 unrelated Japanese patients with FECD, and 5 patients with PPMD using polymerase chain reaction and direct sequencing. Mutation screenings were also performed in 36 unrelated normal volunteers as controls, as well as slit-lamp and specular microscopy.


RESULTS
Two types of heterozygous missense mutations of the COL8A2 gene (R155Q and T502M) in 5 of 15 FECD probands (R155Q, 3/30 chromosomes, 10.0%; T502M, 3/30 chromosomes, 10.0%) were found. No mutation was detected in the coding region of the COL8A2 gene in the remaining 10 patients with FECD nor in any of the 5 patients with PPMD. These two mutations were also found in normal Japanese volunteers (R155Q, 5/72 chromosomes, 6.9%; T502M, 11/70 chromosomes, 15.7%). The chromosomal frequency of the two mutations was not significant between the patients and normal controls.


CONCLUSIONS
The R155Q and T502M mutations of COL8A2 may not be the causative defect in the Japanese FECD and PPMD patients examined in this study.
Kobayashi
Akira
A
Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. kobaya@kenroku.kanazawa-u.ac.jp
Fujiki
Keiko
K
Murakami
Akira
A
Kato
Takuji
T
Chen
Li-Zhong
LZ
Onoe
Hitoshi
H
Nakayasu
Kiyoo
K
Sakurai
Mayumi
M
Takahashi
Mami
M
Sugiyama
Kazuhisa
K
Kanai
Atsushi
A
D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D024102:Collagen Type VIII / Q000235:genetics*; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics*; D005787:Gene Frequency; D005973:Glutamine / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D013912:Threonine / Q000235:genetics
C443712:COL8A2 protein, human; D024102:Collagen Type VIII; D005973:Glutamine; D013912:Threonine; D001120:Arginine; D008715:Methionine