In a Canadian patient with early-onset glaucoma and a strong family history of autosomal dominant glaucoma with variable age at onset (GLC1A; 137750), Vincent et al. (2002) found a gly399-to-val mutation in the MYOC gene (G399V; 601652.0013) and a 7940G-A transition in exon 3 of the CYP1B1 gene, resulting in an arg368-to-his (R368H) mutation. All participants with glaucoma in this family carried the G399V mutation. Individuals carrying both the CYP1B1 and MYOC mutations had juvenile-onset open angle glaucoma with a mean age at onset of 27 years (range, 23 to 38 years). Individuals with only the MYOC mutation had a mean age at onset of 51 years (range, 48 to 64 years). The R368H mutation had previously been reported by Bejjani et al. (2000) in homozygosity in Saudi Arabian patients with congenital glaucoma (GLC3A; 231300) with incomplete penetrance and was not found in 100 Saudi Arabian control chromosomes.
Vincent et al. (2002) identified the R368H mutation in 1 of 140 (0.7%) control subjects. The individual was of Saudi Arabian descent and had autosomal recessive retinitis pigmentosa but no glaucoma.
In 2 Roma/Gypsy probands with congenital glaucoma, Azmanov et al. (2011) identified heterozygosity for the R368H mutation in the CYP1B1 gene; 1 of the patients was also heterozygous for the Gypsy founder mutation R299X in the LTPB2 gene (602091.0001). The authors stated that the pathogenicity of R368H in these patients was uncertain.
Pasutto et al. (2010) detected marked reduction in enzymatic activity of CYP1B1 carrying the R368H mutation in in vitro functional assays.
Lek et al. (2016) noted a high allele frequency (0.0294) of this variant in the South Asian population in the ExAC database.