Clinical phenotype of posterior polymorphous corneal dystrophy in a family with a novel ZEB1 mutation.
OBJECTIVE
To describe the clinical phenotype in a family with posterior polymorphous corneal dystrophy (PPCD) and a novel mutation in the ZEB1 gene.


METHODS
Clinical examination, anterior segment photography, specular microscopy and electrophysiological investigations were performed and quantified. Genomic DNA extracted from peripheral blood was sequenced for ZEB1 exons. Cosegregation of identified mutation with the disease status in the family was confirmed using polymerase chain reaction and restriction fragment length polymorphism.


RESULTS
Ocular examination was performed on five family members from two generations. Three had anomalies of the corneal endothelium that were consistent with PPCD. Endothelial cell counts ranged from 2306 to 2987 mm(2) (ref. 2000-4000 cells/mm(2) ). No evidence of glaucoma or retinal abnormalities was observed. Extraocular abnormalities such as inguinal herniation, hydrocoele and possible bony or connective tissue anomalies were part of the disease spectrum in this family. Mutation analysis revealed a novel change in exon 5 of ZEB1 (c.672delA) that cosegregated with the affected disease status.


CONCLUSIONS
The detailed clinical features of PPCD associated with a novel ZEB1 mutation are supportive of the previously proposed range of phenotype parameters. Further phenotype-genotype correlations may provide insights into the clinical variability and pathological processes affecting the corneal endothelium, Descemet's membrane, retinal photoreceptor function and extraocular tissues of some patients.
Nguyen
Dan Q
DQ
Department of Ophthalmology, Bristol Eye Hospital, UK.
Hosseini
Mohsen
M
Billingsley
Gail
G
Héon
Elise
E
Churchill
Amanda J
AJ
D000293:Adolescent; D000328:Adult; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D055954:Corneal Endothelial Cell Loss / Q000235:genetics; D004252:DNA Mutational Analysis; D004728:Endothelium, Corneal / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014157:Transcription Factors / Q000235:genetics*; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1