Fig. 1 Phenotype/genotype correlation studies of the K423E TIGR mutation in pedigree GV-001. a, Phenotypic status and segregation analysis of TIGRK423E in branch GV-510. Complete ophthalmologic examinations were performed yearly for the past five years in all members of branch GV-510 as described11. Criteria for POAG were intraocular pressures (IOP) above 22 mm Hg in both eyes, characteristic optic disk damage and/or visual field impairment and grade III or IV (open-angle) gonioscopy. Subjects with IOP above 22 mm Hg in both eyes but no other signs of glaucoma were diagnosed with OHT. Open symbols, unaffected individuals; solid black symbols, POAG, either juvenile or adult-onset; gray symbol, OHT; symbols with a black quadrant, deceased subjects reported as blind; OD, right eye; OS, left eye. Visual fields: N, normal; ND, not determined. Impairments are represented by vertical arrows:↓, arcuate scotomas or nasal step;↓↓, advanced arcuate scotomas; NA, not available. Disk appearance is given by cup-to-disk ratio on a scale of 0.1 (healthy) to 1.0 (damaged). The founder of the pedigree, person I-1 (ref. 11), is shown at the top. An ARMS test was designed for the A→ G transition at nt 1332 of the mRNA as described12. Primer sequences may be obtained from the authors upon request. ARMS results are depicted below each symbol. Genotypes of mutant homozygotes are highlighted on a black background. Parental origin of the disease allele was determined by haplotype analyses, as described11. The right side of each genotype depicts the allele inherited from the father, the left side presents the allele inherited from the mother. b, Penetrance rate of TIGRK423E in heterozygous carriers. The penetrance rate of the mutation, defined as the number of affected persons (either OHT or POAG)/the number of heterozygotic carriers, was estimated in pedigree GV-001 excluding members of branch GV-510 for three groups of ages (middle column). Age at onset was defined as age when OHT was diagnosed in individuals who had yearly tonometry to detect early signs of glaucoma (55/98 heterozygotes, of which 47 later developed POAG) or as age when POAG was diagnosed (32/98 heterozygotes). Eleven of these 98 heterozygotes were asymptomatic. Identical procedures were done for heterozygotes in generations V to VII of branch GV-510 (right column). Father V-2 (Fig. 1a) was included in the 20− 39 years of age group because an ocular examination recorded in 1963 showed that he had advanced POAG at age 42. a b