Primary congenital glaucoma caused by the homozygous F261L CYP1B1 mutation and paternal isodisomy of chromosome 2.

Primary congenital glaucoma (PCG), a rare, severe and blinding disease, usually results from mutations in the CYP1B1 gene located in chromosome 2p22.2. Uniparental isodisomy (UPID) is also a rare condition in which a diploid offspring carries two identical copies of a single parental chromosome. By DNA sequence analysis, we found that a proband (female newborn) affected by PCG was homozygous for the null-allele F261L of the CYP1B1 gene. Her father was a heterozygous carrier for this mutation, and unexpectedly her mother carried only the G168D mutation in the heterozygous state. Segregation analysis of eight microsatellite markers which spanned the two arms of chromosome 2 was consistent with paternal isodisomy for this chromosome in the proband. To the best of our knowledge, this is the first reported case of UPID resulting in PCG and the fifth reported case of paternal UPID for chromosome 2. In addition, the absence of a clinical phenotype other than PCG confirms previous observations of there being no paternally imprinted genes in chromosome 2 that have major phenotypic effects. These results, along with previous reports, also suggest that UPID may play a relevant role in recessive diseases linked to chromosome 2.