See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on allelic variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

The probability of identifying pathogenic variants in CYP1B1 increases with the presence of: positive family history, parental consanguinity, and bilateral and severe disease. Differences in the number of individuals studied, the methods of ascertainment (familial vs simplex cases, unilateral vs bilateral disease), and the molecular genetic testing methods used make accurate estimates of variant detection frequency difficult.

Mashima et al [2001], Stoilov et al [2002], Curry et al [2004]

At least five CYP1B1 alleles with gross deletions, sometimes including the entire CYP1B1 along with adjacent genes, have been reported. Additionally, gross duplications and a complex mutational event are known. For details see Molecular Genetics, Table A, Locus-Specific Databases and HGMD.

Ali et al [2009], Narooie-Nejad et al [2009], Micheal et al [2016]

No data on detection rate of gene-targeted deletion/duplication analysis are available.

Heterozygous TEK pathogenic variants were identified in affected individuals from 10/189 unrelated families with PCG [Souma et al 2016].

Kaur et al [2005] presented evidence in a single individual that the combination of a heterozygous pathogenic variant in MYOC and a heterozygous pathogenic variant in CYP1B1 was associated with PCG, suggesting digenic inheritance. A report of a Chinese family segregating both primary congenital open-angle glaucoma (POAG) and PCG suggested that homozygous MYOC variants may cause PCG [Zhuo et al 2006].

Two additional loci, GLC3B on 1p36 [Akarsu et al 1996] and GLC3C on 14q24.3 [Stoilov & Sarfarazi 2002], have been linked to PCG; however, the genes at these loci are not known. One additional locus linked to PCG, on 14q24.2-q24.3, does not appear to overlap the GLC3C critical region [Firasat et al 2008].