Molecular basis of Peters anomaly in Saudi Arabia.
Peters anomaly (PA) and primary congenital glaucoma (PCG) are genetically and phenotypically distinct conditions. Mutations in cytochrome P4501B1 (CYP1B1) are the most common cause of PCG in Saudi Arabia. Recent evidence suggests that there may be common genetic factors to these conditions. To determine the molecular basis of PA, 11 study subjects with PA from 10 Saudi Arabian families were recruited. Experienced ophthalmologists examined all affected subjects and most of their available unaffected relatives. The diagnosis of PA was confirmed by pathological examination of excised corneal buttons in seven subjects. The coding exons of FOXC1, PITX2, and PAX6 were screened and those of CYP1B1 and FOXE3 sequenced. Homozygous CYP1B1 mutations were identified in six individuals in five families. Five individuals were homozygous for G61E and one was homozygous for 143del10. No mutations were identified in FOXC1, PITX2, PAX6, or FOXE3. The clinical or pathologic phenotype of the subjects with CYP1B1 mutations was not different from that of the other PA patients in this study. Two families included at least one individual with homozygous CYP1B1 mutations and no ocular anomalies (nonpenetrant). Mutations in CYP1B1 may be a substantive cause for PA in this population. Thus, PA and PCG may share a common molecular pathophysiology. Indeed, PA and PCG may share the same spectrum of anterior segment dysgenesis. Finally, the occurrence of PA, PCG, and unaffected individuals with identical homozygous CYP1B1 mutations in the same sibship suggests the presence of modifiers that modulate the clinical severity of the phenotypic expression of the same CYP1B1 mutation(s).
Edward
Deepak
D
Department of Ophthalmology and Visual Sciences and Pathology, University of Illinois College of Medicine, Chicago, USA.
Al Rajhi
Ali
A
Lewis
Richard Alan
RA
Curry
Stacey
S
Wang
Zongren
Z
Bejjani
Bassem
B
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015415:Biomarkers; D003318:Corneal Opacity / Q000235:genetics / Q000473:pathology; D065633:Cytochrome P-450 CYP1B1; D004268:DNA-Binding Proteins / Q000235:genetics; D005136:Eye Proteins; D005260:Female; D051858:Forkhead Transcription Factors; D005901:Glaucoma / Q000151:congenital / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010375:Pedigree; D012097:Repressor Proteins; D012529:Saudi Arabia; D014157:Transcription Factors / Q000235:genetics; D000097577:Homeobox Protein PITX2
D001189:Aryl Hydrocarbon Hydroxylases; D015415:Biomarkers; D065633:Cytochrome P-450 CYP1B1; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C112743:FOXC1 protein, human; C404285:FOXE3 protein, human; C000605730:PAX6 protein, human; C585496:CYP1B1 protein, human