Pro370Leu MYOC gene mutation in a large Chinese family with juvenile-onset open angle glaucoma: correlation between genotype and phenotype.
OBJECTIVE
Glaucoma is the leading cause of irreversible blindness worldwide. Most of the cases are primary open angle glaucoma (POAG). POAG is a genetically heterogenous disease; autosomal dominance is the most frequent type of monogenic inheritance. In this study, we identified the genotype of a MYOC mutation and investigated the phenotype of a Chinese juvenile-onset open angle glaucoma (JOAG) pedigree (GZ.1 pedigree).


METHODS
Blood samples were obtained from 24 participants. We performed sequence and gene linkage analysis in the GZ.1 pedigree retrospectively. Comprehensive ophthalmologic examinations were performed for each family member. Pharmacological treatment or filtering surgery was performed as needed according to the intraocular pressure (IOP) of each individual.


RESULTS
A Pro370Leu myocilin mutation located in exon 3 of MYOC was identified in 24 members of the GZ.1 pedigree. Sixteen patients had juvenile-onset primary open-angle glaucoma (JOAG), and the others participating in the project had no such genotype. Analysis of polymorphic microsatellite markers indicated that the disease in GZ.1 is autosomal dominant inheritance. The patients in GZ.1 are characterized by early age of onset (before 35 years of age), severe clinical presentations, and high intraocular pressure unresponsive to pharmacological treatment; requiring 89.5% of the patients to undergo filtering surgery. Fortunately, the success rate of surgery was high. None of the patients required further medical treatment and only one demonstrated low IOP fundus changes.


CONCLUSIONS
This is the first evidence of a founder effect for a Pro370Leu myocilin mutation in a Chinese POAG pedigree. The family with the Pro370Leu myocilin mutation presents with juvenile-onset glaucoma. After 10 years of follow-up, it is evident that the mutation is closely associated with the phenotype of the patients. Analysis of MYOC in JOAG patients may enable the identification of at-risk individuals and help prevent disease progression toward the degeneration of the optic nerve, and may also contribute to genetic counseling.
Zhuo
Ye-Hong
YH
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
Wei
Yan-Tao
YT
Bai
Yu-Jing
YJ
Duan
Shan
S
Lin
Ming-Kai
MK
Saragovi
H Uri
HU
Ge
Jian
J
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D005123:Eye / Q000473:pathology; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005190:Family; D005260:Female; D005902:Glaucoma, Open-Angle / Q000453:epidemiology* / Q000235:genetics*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011392:Proline / Q000235:genetics*; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D007930:Leucine; D011392:Proline; D000099179:Myocilin