TY - JOUR

T1 - CYP1B1 Mutations in Individuals With Primary Congenital Glaucoma and Residing in Denmark

AU - Gronskov, Karen

AU - Redo-Riveiro, Alba

AU - Sandfeld, Lisbeth

AU - Zibrandtsen, Nathalie

AU - Harris, Pernille

AU - Bach-Holm, Daniella

AU - Tümer, Zeynep

PY - 2016/12

Y1 - 2016/12

N2 - Purpose of the Study: Primary congenital glaucoma (PCG OMIM 231300) can be caused by pathogenic sequence variations in cytochrome P450, subfamily 1, polypeptide 1 (CYP1B1). The purpose of this study was to investigate the contribution of sequence variations in CYP1B1 in a cohort of individuals with PCG residing in Denmark.Methods: The study included 37 unrelated individuals with PCG. Individuals were investigated for CYP1B1 mutations by Sanger sequencing of polymerase chain reaction products using BigDye terminators and capillary electrophoresis.Results: A total of 12 mutations were identified and 5 of these were novel. Six were missense mutations; 4 were truncating mutations (2 nonsense and 2 frameshift); 1 was an in-frame deletion and 1 was an in-frame duplication. Mutations in CYP1B1 could fully explain the PCG phenotype in 7 individuals (18%). Five individuals were compound heterozygous or presumed compound heterozygous, 1 was homozygous and 1 was apparently homozygous. Three individuals were heterozygous for sequence variations in CYP1B1 thought to be pathogenic—one of these was p.(Tyr81Asn). Several known sequence variations with presumably no functional effect were found in the cohort.Conclusions: In this study, we identified 12 CYP1B1 mutations, 5 of which were novel. The frequency of CYP1B1 mutations in this cohort was comparable with other populations. We also detected an individual heterozygous for p.(Tyr81Asn) mutation, previously suggested to cause autosomal dominant primary open-angle glaucoma.

AB - Purpose of the Study: Primary congenital glaucoma (PCG OMIM 231300) can be caused by pathogenic sequence variations in cytochrome P450, subfamily 1, polypeptide 1 (CYP1B1). The purpose of this study was to investigate the contribution of sequence variations in CYP1B1 in a cohort of individuals with PCG residing in Denmark.Methods: The study included 37 unrelated individuals with PCG. Individuals were investigated for CYP1B1 mutations by Sanger sequencing of polymerase chain reaction products using BigDye terminators and capillary electrophoresis.Results: A total of 12 mutations were identified and 5 of these were novel. Six were missense mutations; 4 were truncating mutations (2 nonsense and 2 frameshift); 1 was an in-frame deletion and 1 was an in-frame duplication. Mutations in CYP1B1 could fully explain the PCG phenotype in 7 individuals (18%). Five individuals were compound heterozygous or presumed compound heterozygous, 1 was homozygous and 1 was apparently homozygous. Three individuals were heterozygous for sequence variations in CYP1B1 thought to be pathogenic—one of these was p.(Tyr81Asn). Several known sequence variations with presumably no functional effect were found in the cohort.Conclusions: In this study, we identified 12 CYP1B1 mutations, 5 of which were novel. The frequency of CYP1B1 mutations in this cohort was comparable with other populations. We also detected an individual heterozygous for p.(Tyr81Asn) mutation, previously suggested to cause autosomal dominant primary open-angle glaucoma.

KW - primary congenital glaucoma

KW - CYP1B1

KW - mutation screening

U2 - 10.1097/IJG.0000000000000581

DO - 10.1097/IJG.0000000000000581

M3 - Journal article

C2 - 27820421

VL - 25

SP - 926

EP - 930

JO - Journal of Glaucoma

JF - Journal of Glaucoma

SN - 1057-0829

IS - 12

ER -