Myocilin mutations in a population-based sample of cases with open-angle glaucoma: the Rotterdam Study

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 240; no. 6; pp. 468 - 474
• Main Authors: HULSMAN, Caroline A. A, DE JONG, Paulus T. V. M, LETTINK, Marjolein, VAN DUIJN, Cornelia M, HOFMAN, Albert, BERGEN, Arthur A. B
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.06.2002; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Cytoskeletal Proteins; DNA Mutational Analysis; Eye Proteins - genetics; Female; Glaucoma; Glaucoma and intraocular pressure; Glaucoma, Open-Angle - epidemiology; Glaucoma, Open-Angle - genetics; Glycoproteins - genetics; Humans; Male; Medical sciences; Middle Aged; Netherlands - epidemiology; Ophthalmology; Pedigree; Point Mutation; Prevalence; Netherlands; Human; Eye disease; Myocilin; Prevalence; Open angle glaucoma; Gene; Family study; Molecular epidemiology; Mutation; Genetic determinism
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-002-0455-1

To investigate the prevalence of myocilin (MYOC) mutations in a population-based sample of open-angle glaucoma (OAG) cases and to describe a family with both juvenile and adult onset OAG caused by a mutation in MYOC. MYOC was screened in cases derived from the Rotterdam Study in the Netherlands. Definite OAG was defined as a glaucomatous optic neuropathy together with a glaucomatous visual field defect. Upon the identification of the Asn480Lys mutation in one case, seven additional family members were studied. To test for a founder effect with earlier reported families with this mutation, the haplotypes of MYOC flanking markers D1S2851, D1S242, D1S218, and D1S1165 were compared. Seven sequence alterations in MYOC were found in 14 of 47 OAG cases; six of these were also found in controls. In one case, an Asn480Lys mutation was found. In relatives of the latter patient, the phenotype ranged from a glaucomatous optic neuropathy without visual field defect in a 70-year-old patient to severely affected optic discs and a remaining temporal remnant in a 34-year-old patient; those without the mutation had no signs of OAG. Haplotype analysis suggested a different origin of the mutation. The prevalence of MYOC mutations (2.2%) was similar to that found in hospital-based studies. Although mutations in MYOC are rare, relatives carrying this mutation run a high risk of developing the disease. Instead of submitting all members of a family with the Asn480Lys mutation to frequent follow-up, medical care can be restricted to those carrying the mutation.