CYP1B1, MYOC, and LTBP2 Mutations in Primary Congenital Glaucoma Patients in the United States

Purpose To screen primary congenital glaucomapatients in the United States for sequence variants within the CYP1B1, LTBP2 , and MYOC genes using Sanger and whole exome sequencing. Design Retrospective case-control study. Methods Fifty-seven primary congenital glaucomapatients (47 families), 71 unaffected family members of the primary congenital glaucoma probands, and 101 healthy unrelated individuals were recruited from a single institution. Sanger sequencingof the primary congenital glaucomagene, CYP1B1, was performed on 47 probanddeoxyribonucleic acid samples. Simultaneously, whole exome sequencingwas conducted on 3 families, each including more than 1 affected individual. Concurrently, 33 of 47 primary congenital glaucoma probandswith extended familydeoxyribonucleic acid samples were screened for LTBP2 and MYOC gene mutations. Exome-sequenced variations were validated by additional Sanger sequencingto confirm segregation of filtered disease-causing single nucleotide variations. Results Seven primary congenital glaucomafamilies (14.9%) manifested disease phenotypes attributable to CYP1B1mutations. One primary congenital glaucomafamily possessed homozygous mutant alleles, whereas 6 families carried compound heterozygous mutations. Five novel combinations of compound heterozygous mutations were identified, of which 2 combinations were found with whole exome sequencing. No disease-causing mutations within the LTBP2 and MYOC genes were discovered. Conclusions This study analyzed CYP1B1, LTBP2 , and MYOC mutations in a cohort of primary congenital glaucomapatients from the United States, applying whole exome sequencingas a complementary tool to Sanger sequencing. Whole exome sequencing, coupled with Sanger sequencing, may identify novel genes in primary congenital glaucomapatients who have no mutations in known primary congenital glaucomagenes.