title: Pro370Leu myocilin mutation in a Chinese pedigree with juvenile-onset open angle glaucoma.
abstract: OBJECTIVE
  To investigate the genotype and phenotype of juvenile-onset open angle glaucoma (JOAG) in a Chinese family (PN pedigree).
  
  
  METHODS
  Each family member was comprehensively examined by an experienced ophthalmologist. The clinical characteristics of the family patients with JOAG were documented. Blood samples were obtained from 22 available participants from the PN pedigree. Linkage analysis was performed to identify the possible chromosome loci. The presence of gene mutation was ascertained by polymerase chain reaction amplification and subsequent direct sequencing.
  
  
  RESULTS
  The affected members in the PN pedigree are characterized by early age of onset (mean age at diagnosis is 17 years old), severe clinical presentations, high intraocular pressure (mean IOP of 34.18±2.97 mmHg), and poor response to pharmacological treatment (87.5% of the patients required filtering surgery). The region on chromosome 1 between D1S3464 and D1S1619 was identified in this pedigree by linkage analysis. A Pro370Leu myocilin mutation resulting from a heterozygous C→T transition at the 1,109th nucleotide in exon 3 was detected by gene sequencing. The Pro370Leu mutation co-segregated among all affected individuals of PN pedigree.
  
  
  CONCLUSIONS
  The GLC1A Pro370Leu mutation is firmly correlated with a severe POAG phenotype. These data provide clues for the severe disease-causing nature of the Pro370Leu allele. Gene screening may be a useful method for pre-symptom diagnosis and a forewarning to detect the at-risk individuals in familial open-angle glaucoma patients, especially in pedigrees of early-onset.
authors.affiliation: Visual Science Lab, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People’s Republic of China.
authors.forename: Yan-Tao
authors.initials: YT
authors.lastname: Wei
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Li
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Bai
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Jun-Hong
authors.initials: JH
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
authors.forename: Ye-Hong
authors.initials: YH
authors.lastname: Zhuo
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D056426:Genetic Loci; D005820:Genetic Testing; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009798:Ocular Hypertension / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin