Primary congenital glaucoma: a novel single-nucleotide deletion and varying phenotypic expression for the 1,546-1,555dup mutation in the GLC3A (CYP1B1) gene in 2 families of different ethnic origin.
OBJECTIVE
To present new molecular genetic data on primary congenital glaucoma from 2 families, 1 isolated case and 3 familial cases due to mutations in the cytochrome P-450 1B1 (CYP1B1) gene.


METHODS
All diagnoses were made by slit-lamp biomicroscopy, gonioscopy, cornea and optic disk measurements, ultrasound-biometry, and automated static threshold perimetry where possible. Mutation screening was performed by direct sequence analysis of DNA extracted from peripheral blood of the patients and their relatives.


RESULTS
For the isolated case, a child of 4 years, a homozygous nucleotide deletion within a tetrad of cytosines (nt622-625, 622delC) was found leading to a predicted nonsense codon 93 truncating the protein by 450 amino acids. For the familial cases, the 3 affected members showed a homozygous mutation 1,546-1,555dupTCATGCCACC for which 9 healthy relatives proved to be heterozygous. The phenotypic expression of these 3 patients varied widely.


CONCLUSIONS
Our results confirm the crucial role of CYP1B1 mutations for congenital glaucoma.
Soley
Gabriela Chavarria
GC
Escuela de Biología, Universidad de Costa Rica.
Bosse
Kristin A
KA
Flikier
David
D
Flikier
Paul
P
Azofeifa
Jorge
J
Mardin
Christian Y
CY
Reis
Andre
A
Michels-Rautenstrauss
Karin G
KG
Rautenstrauss
Bernd W
BW
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D003241:Consanguinity; D003364:Costa Rica / Q000453:epidemiology; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D005901:Glaucoma / Q000151:congenital* / Q000208:ethnology / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D014421:Turkey / Q000453:epidemiology; D014794:Visual Fields
D018389:Codon, Nonsense; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1