Clinical features associated with an Asp380His Myocilin mutation in a US family with primary open-angle glaucoma.
OBJECTIVE
To determine the glaucoma phenotype of an American pedigree with the myocilin Asp380His.


METHODS
An observational case series study.


METHODS
An observational case series study was used to examine a family in which an Asp380His myocilin mutation was segregating. Thirteen family members were examined and medical records were obtained on the remaining two individuals. Blood samples were collected from all 15 participants following the tenets of the Helsinki declaration under the auspices of the Oregon Health & Sciences University Institutional Review Board and screened for myocilin variants by denaturing high-performance liquid chromatography (dHPLC). Any DNA samples with dHPLC data different from the control sample were sequenced for base pair analysis.


RESULTS
An Asp380His myocilin mutation was identified in eight members, seven of whom had primary open-angle glaucoma (POAG). The eighth individual had high intraocular pressures (IOPs). The disease presents in this family with extremely high IOPs requiring trabeculectomies to control the pressure. The age at diagnosis ranged from 30 to 45.


CONCLUSIONS
This family with an Asp380His myocilin mutation presents with an intermediate phenotype between juvenile- and adult-onset glaucoma. The Asp380 amino acid residue appears to be important in myocilin function based on the finding that substitution of this amino acid with four different amino acids (His, Ala, Asn, or Gly) all result in a similar presentation of POAG that is intermediate between the more severe clinical presentations observed in individuals with the Pro370Leu or Lys423Glu variant and the milder findings in patients with the Gln368Stop mutation.
Wirtz
Mary K
MK
Casey Eye Institute, Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon 97239, USA. wirtzm@ohsu.edu
Samples
John R
JR
Choi
Dongseok
D
Gaudette
N Donna
ND
D000328:Adult; D001224:Aspartic Acid / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D006023:Glycoproteins / Q000235:genetics*; D006639:Histidine / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014130:Trabeculectomy; D000099179:Myocilin
D001224:Aspartic Acid; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D006639:Histidine; D000099179:Myocilin