Novel mutations in the ZEB1 gene identified in Czech and British patients with posterior polymorphous corneal dystrophy.
We describe the search for mutations in six unrelated Czech and four unrelated British families with posterior polymorphous corneal dystrophy (PPCD); a relatively rare eye disorder. Coding exons and intron/exon boundaries of all three genes (VSX1, COL8A2, and ZEB1/TCF8) previously reported to be implicated in the pathogenesis of this disorder were screened by DNA sequencing. Four novel pathogenic mutations were identified in four families; two deletions, one nonsense, and one duplication within exon 7 in the ZEB1 gene located at 10p11.2. We also genotyped the Czech patients to test for a founder haplotype and lack of disease segregation with the 20p11.2 locus we previously described. Although a systematic clinical examination was not performed, our investigation does not support an association between ZEB1 changes and self reported non-ocular anomalies. In the remaining six families no disease causing mutations were identified thereby indicating that as yet unidentified gene(s) are likely to be responsible for PPCD.
Liskova
Petra
P
Division of Molecular Genetics, Institute of Ophthalmology, UCL, London, United Kingdom. p.liskova@ucl.ac.uk
Tuft
Stephen J
SJ
Gwilliam
Rhian
R
Ebenezer
Neil D
ND
Jirsova
Katerina
K
Prescott
Quincy
Q
Martincova
Radka
R
Pretorius
Marike
M
Sinclair
Neil
N
Boase
David L
DL
Jeffrey
Margaret J
MJ
Deloukas
Panos
P
Hardcastle
Alison J
AJ
Filipec
Martin
M
Bhattacharya
Shomi S
SS
D000293:Adolescent; D000328:Adult; D000368:Aged; D024102:Collagen Type VIII / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D018153:Czech Republic; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D035583:Rare Diseases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D006113:United Kingdom; D000071799:Zinc Finger E-box-Binding Homeobox 1
C443712:COL8A2 protein, human; D024102:Collagen Type VIII; D005136:Eye Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C491583:VSX1 protein, human; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1