Mutations in the myocilin gene in families with primary open-angle glaucoma and juvenile open-angle glaucoma.
OBJECTIVE
To investigate the prevalence of myocilin (MYOC) mutations in Italian families with glaucoma and to determine the relationship of these mutations to primary open-angle glaucoma (POAG), juvenile open-angle glaucoma (JOAG), and pigmentary dispersion glaucoma.


METHODS
Twenty-six patients with POAG were selected based on a positive family history of glaucoma. All patients and 210 relatives had an accurate clinical characterization.


METHODS
Each index patient was screened by single-stranded conformational polymorphism analysis for mutations in the MYOC gene.


RESULTS
A MYOC gene mutation was found in 2 families. In one family, a previously reported p.K423E mutation was transmitted from the index patient with POAG to the 2 sons with JOAG. In the second family, a p.C25R change, affecting the signal peptide, was transmitted from the index patient with POAG to the son with JOAG, but not to the son with pigmentary dispersion glaucoma.


CONCLUSIONS
Clinical characterization of 2 families with MYOC gene mutations indicates that POAG and JOAG are the 2 sides of a continuum phenotypical spectrum due to a common molecular defect. On the other hand, our results confirm the different origin of pigmentary dispersion glaucoma.


CONCLUSIONS
Because MYOC gene mutations may be responsible for a fraction (2 [8%] of 26) of families with POAG/JOAG, a molecular genetic diagnosis should be included in the management of patients with glaucoma.
Bruttini
Mirella
M
Division of Medical Genetics, Department of Molecular Biology, University of Siena, Siena, Italy.
Longo
Ilaria
I
Frezzotti
Paolo
P
Ciappetta
Rossella
R
Randazzo
Alessandro
A
Orzalesi
Nicola
N
Fumagalli
Elena
E
Caporossi
Aldo
A
Frezzotti
Renato
R
Renieri
Alessandra
A
D000328:Adult; D000368:Aged; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin