Clinical Feature Aociated With an Ap380Hi Myocilin Mutation in a U Family With Primary Open-Angle Glaucoma Original Reearch Article

Purpoe To determine the glaucoma phenotype of an American pedigree with the myocilin Ap380Hi. Deign An obervational cae erie tudy. Method An obervational cae erie tudy wa ued to examine a family in which an Ap380Hi myocilin mutation wa egregating. Thirteen family member were examined and medical record were obtained on the remaining two individual. Blood ample were collected from all 15 participant following the tenet of the Helinki declaration under the aupice of the Oregon Health & cience Univerity Intitutional Review Board and creened for myocilin variant by denaturing high-performance liquid chromatography (dHPLC). Any DNA ample with dHPLC data different from the control ample were equenced for bae pair analyi. Reult An Ap380Hi myocilin mutation wa identified in eight member, even of whom had primary open-angle glaucoma (POAG). The eighth individual had high intraocular preure (IOP). The dieae preent in thi family with extremely high IOP requiring trabeculectomie to control the preure. The age at diagnoi ranged from 30 to 45. Concluion Thi family with an Ap380Hi myocilin mutation preent with an intermediate phenotype between juvenile- and adult-onet glaucoma. The Ap380 amino acid reidue appear to be important in myocilin function baed on the finding that ubtitution of thi amino acid with four different amino acid (Hi, Ala, An, or Gly) all reult in a imilar preentation of POAG that i intermediate between the more evere clinical preentation oberved in individual with the Pro370Leu or Ly423Glu variant and the milder finding in patient with the Gln368top mutation.