The novel Y371D myocilin mutation causes an aggressive form of juvenile open-angle glaucoma in a Caucasian family from the Middle-East.
OBJECTIVE
To search for the genetic cause of juvenile open-angle glaucoma (JOAG) in a Caucasian family and to perform genotype/phenotype correlation studies in the kindred.


METHODS
Six members of a three-generation family originating from Uzbekistan and now living in the Middle East were recruited from one large clinic in Israel. Ophthalmologic investigations comprised of visual field assessments, intraocular pressure measurements, optic disc evaluation, and gonioscopy. Medical charts were obtained to date the onset of glaucoma and to evaluate aggressivity of the trait. We screened the myocilin gene (MYOC, OMIM 601652) by direct genomic sequencing of its three exons in all family members.


RESULTS
JOAG segregated as an autosomal dominant trait in four members of the family. The proband, a 14-year-old girl, had been diagnosed with juvenile open-angle glaucoma at 12 years old. Her mother, maternal aunt, and maternal grandfather all had JOAG that started at an early age. The disorder progressed rapidly even under optimal medical treatment, and all four patients had to undergo trabeculectomy. One missense mutation, Y371D (1111t-->g, Tyr [Y] 371 Asp [D]), was identified. This mutation cosegregated with the disorder in all affected members and was absent in 200 Caucasian controls. The Y371D MYOC mutation has not been reported before. One cousin of the proband was a silent heterozygotic carrier of the mutation and was still asymptomatic at nine years of age.


CONCLUSIONS
We identified a novel mutation (Y371D) in MYOC from a Caucasian family who presented with an aggressive form of JOAG that required early trabeculectomy. Genetic screening of the MYOC mutation was beneficial in predicting one asymptomatic heterozygotic carrier.
Avisar
Inbal
I
Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel. avisar.inbal@gmail.com
Lusky
Moshe
M
Robinson
Anat
A
Shohat
Mordechai
M
Dubois
Stéphane
S
Raymond
Vincent
V
Gaton
Dan D
DD
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D020090:Chromosome Segregation; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008877:Middle East; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D044465:White People / Q000235:genetics*; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin