Screening for mutations of Axenfeld-Rieger syndrome caused by FOXC1 gene in Japanese patients.
OBJECTIVE
Mutations in the forkhead transcription factor gene (FOXC1) have been recently shown to cause some cases of juvenile glaucoma associated with a variety of anterior-segment anomalies. The purpose of this study was to investigate the clinical features of Axenfeld-Rieger syndrome caused by FOXC1 mutations in Japanese patients.


METHODS
After informed consent was obtained, genomic DNA was isolated from peripheral blood. The DNA-sequence changes were analyzed using single-strand conformation polymorphism analysis and automated sequencing in six Japanese probands with Axenfeld-Rieger syndrome.


RESULTS
The authors identified four mutations: pedigree 1 (26-47ins22), 2 (Ile91Ser), 3 (286ins1), and 4 (Arg127His). Two pedigrees showed new mutations in FOXC1. In pedigrees 1,2, and 4, younger generations had iris hypoplasia with severe early-onset glaucoma, whereas their parents had posterior embryotoxon without glaucoma. Pedigree 3 had a single affected person with iris hypoplasia and posterior embryotoxon with a mild increase of intraocular pressure.


CONCLUSIONS
Four different FOXC1 mutations were found in four of six Japanese pedigrees with Axenfeld-Rieger syndrome. This was a new mutation in two pedigrees that was not found in earlier generations. This study confirms that mutations in this gene cause maldevelopment of the anterior segment of the eye.
Kawase
C
C
Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
Kawase
K
K
Taniguchi
T
T
Sugiyama
K
K
Yamamoto
T
T
Kitazawa
Y
Y
Alward
W L
WL
Stone
E M
EM
Nishimura
D Y
DY
Sheffield
V C
VC
D000293:Adolescent; D000595:Amino Acid Sequence; D000869:Anterior Eye Segment / Q000002:abnormalities*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005124:Eye Abnormalities / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D005260:Female; D051858:Forkhead Transcription Factors; D005901:Glaucoma / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007223:Infant; D007429:Intraocular Pressure; D007498:Iris / Q000002:abnormalities*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors