[A novel mutation in the myocilin gene identified in a Chinese primary open angle glaucoma family].
OBJECTIVE
To determine the possible myocilin molecular genetic defect underlying POAG in China and to identify the pathogenic mutation causing the disease.


METHODS
The majority of 1 branch of a large Chinese POAG family were personally examined by two senior ophthalmologists. The diagnoses were made by both doctors according to the signs of elevated intraocular pressure, glaucomatous optic neuropathy and glaucomatous visual field defect. All coding sequences of the myocilin gene plus the flanking sites were amplified by polymerase chain reaction (PCR) using genomic DNA from all examined family members followed by sequencing of the PCR products. One hundred normal control subjects were screened by single strand confirmational polymorphism analysis for the mutation.


RESULTS
This Chinese pedigree exhibited autosomal dominant mode of inheritance. The onset age ranged from 26 to 59 years. A novel disease-causing missense mutation T455K in the third exon of the myocilin gene was identified in all affected family members, all glaucoma suspects and 4 individuals who have not shown apparently signs of glaucoma. None of the subjects without the mutation had glaucoma. Affected individuals with the T455K mutation showed variable onset between 26 and 59 years of age. Filtering surgery was performed on all of 7 affected family members. The T455K mutation in myocilin gene was not found in the normal controls. A previously reported polymorphism IVS2+35(A to G)was detected in 4 individuals.


CONCLUSIONS
The novel myocilin sequence alteration T455K that is highly associated with the development of glaucoma and locates in a very conserved residue is proven to be a disease-causing missence mutation. All affected individuals and all POAG suspects in this family are identified to have this mutation. The mutation in this family is associated with a phenotype characterized by mix-onset open angle glaucoma and associated with a high penetrance. It is important for the mutation screening and periodical checkups of presymptomatic individuals belonging to the family of a POAG patient with T455K mutation.
Tian
Qiang
Q
Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, 300020 PR China. qiangtiantj@yahoo.com
Li
Fu-hua
FH
Zhao
Kan-xing
KX
Wang
Li
L
Shan
Xiao-yan
XY
Pang
Yu-ying
YY
Li
Yi-xin
YX
Wu
Mei-jun
MJ
Qiu
Feng
F
Li
Hai-yun
HY
D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D002681:China; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin