Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador.
OBJECTIVE
To determine the role of cytochrome P450IBI (CYP1B1) mutations in causing primary congenital glaucoma (PCG) in a cohort of Native Americans from Quito, Ecuador.


METHODS
Seventeen patients with PCG from 15 Native American families were recruited from the Ophthalmology Clinic at Hospital Metropolitano, Quito, Ecuador. Experienced ophthalmologists examined all affected study subjects. Purified DNA was prepared from peripheral blood samples and CYP1B1 coding exons (exons 2 and 3) were amplified and sequenced. Southern blot was performed only on those affected patients who showed no mutations in the CYP1B1 coding exons.


RESULTS
The molecular basis of PCG in two families was determined: two novel mutations (a deletion and a point mutation) and one novel polymorphism in CYP1B1 were identified in addition to a previously described single amino acid substitution. Southern blot analyses on whole genomic DNA from affected individuals in whom no mutations were identified by the direct PCR/sequencing approach did not detect any large rearrangements or mutations outside the coding region.


CONCLUSIONS
These findings suggest that mutations in CYPIBI are not a major cause of PCG in this population and that at least one additional locus for this condition is responsible for most cases. Further, the PCG phenotype did not correlate readily with the molecular basis of the disorder, suggesting that careful clinical analysis of the phenotype cannot predict the molecular basis of the disease with accuracy.
Curry
Stacey M
SM
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Daou
Aline G
AG
Hermanns
Pia
P
Molinari
Andrea
A
Lewis
Richard Alan
RA
Bejjani
Bassem A
BA
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015139:Blotting, Southern; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D004484:Ecuador / Q000453:epidemiology; D005091:Exons / Q000235:genetics; D005260:Female; D005901:Glaucoma / Q000151:congenital* / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007199:Indians, South American; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1