Primary Congenital Glaucoma: A Novel Single-Nucleotide Deletion and Varying Phenotypic Expression for the 1546–1555dup Mutation in the GLC3A (CYP1B1) Gene in 2 Families of Different Ethnic Origin *#Gabriela Chavarria Soley, MSc, †Kristin A. Bosse, MD, ‡David Flikier, MD, §Paul Flikier, MD, *Jorge Azofeifa, PhD,  Christian Y. Mardin, PD, MD, #Andre Reis, MD, #Karin G. Michels-Rautenstrauss, PhD, and #Bernd W. Rautenstrauss, PD, PhD *Escuela de Biologı ´a and Instituto de Investigaciones en Salud (INISA), Universidad de Costa Rica, ‡Instituto de Cirurgia Ocular, and §Centro Medico de la Vision, San Jose, Costa Rica; †Institute of Human Genetics, Rheinische Friedrich Wilhelm University, Bonn, Germany; and  Department of Ophthalmology and #Institute of Human Genetics, Friedrich-Alexander University, Erlangen, Germany Purpose: 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, cor- nea 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 predict- ed nonsense codon 93 truncating the protein by 450 amino acids. For the familial cases, the 3 affected members showed a homozygous mutation 1546– 1555dupTCATGCCACC for which 9 healthy relatives proved to be heterozygous. The phenotypic expression of these 3 patients varied widely. Conclusion: Our results confirm the crucial role of CYP1B1 mutations for congen- ital glaucoma. Primary congenital glaucoma (PCG) is caused by de- velopmental defects of the Schlemm channel and the trabecular meshwork with a high insertion of the iris root. The disease manifests bilaterally in 70% of patients. Its incidence ranges from 1/12,000 and 1/18,000 live births 1 and represents 1% to 5% of all glaucomas. 2 Males represent 70% of cases. An autosomal-recessive pattern of inheritance is very common in the isolated, primary form with no associated ocular or systemic abnormali- ties. Two chromosomal regions, 2p21 (GLC3A) and 1p36 (GLC3B), are known to be associated with this condi- tion. 3,4 For GLC3A, a series of mutations in the cyto- chrome P-450 1B1 (CYP1B1) gene have been described as the predominant cause of PCG in Turkish, Saudi Ara- bian, and Brazilian families. 5–9 The CYP1B1 gene be- longs to the cytochrome P-450 gene superfamily com- prising more than 300 members, encoding for mono- meric mixed-function monooxygenases. CYP1B1 probably participates in the metabolism of a molecule Received March 18, 2002; sent for revision May 29, 2002; accepted August 26, 2002. This work was supported by the Sonderforschungsbereich Glaukome (SFB539, Deutsche Forschungs Gemeinschaft) and the Johannes und Frieda Marohn Stiftung. GCS was a research fellow of the Deutscher Akademischer Austauschdienst (DAAD). Address correspondence and reprint requests to Bernd W. Rauten- strauss, Institute of Human Genetics, Schwabachanlage 10, D-91054 Erlangen, Germany. E-mail: bernd.rautenstrauss@humgenet.uni- erlangen.de Journal of Glaucoma 12:27–30 © 2003 Lippincott Williams & Wilkins, Inc. 27