Pedigree of patients with juvenile open angle glaucoma (JOAG) caused by a de novo MYOC Val251Ala mutation. Autosomal dominant inheritance of disease is shown in the three-generation pedigree (A). Affected members are represented with filled symbols, with the proband indicated by an arrow. and DNA samples were unavailable from family members (II-1, II-3 and III-2) are indicated by diagonal lines. Two grandparents (I-1 and I-2) in the first generation were disease free, but their daughter (II-2) and three grandchildren (III-1, III-2 and III-3) were all affected. Sequencing of MYOC revealed that all affected individuals in the pedigree (II-2, III-1 and III-3) carry a heterozygous T>C substitution, resulting in an amino acid change Val251Ala (B). Two available normal individuals (I-1 and I-2) in the pedigree have homozygous allele TT in the location (C). Haplotype analysis of 4 polymorphic SNPs within MYOC revealed that the T>C substitution is a de novo mutation (asteriskarrow head) arising in II-2 and transmitted in an autosomal dominant fashion (A). Chromosomal location of the mutation and rs numbers for the genotyped SNPs are indicated (A).