Two novel myocilin mutations in a Chinese family with primary open-angle glaucoma.
OBJECTIVE
To investigate the genetic linkage of primary open-angle glaucoma (POAG) in a Chinese family.


METHODS
We have screened for myocilin (MYOC) gene mutations in a glaucoma family of five generations. There are fifty-six members of whom 11 were confirmed to have POAG , two with ocular hypertension were considered as POAG suspect, and the remaining 43 were asymptomatic. We also recruited 200 unrelated healthy Chinese subjects as normal control. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing were used to identify mutations in the three exons of MYOC. Presymptomatic diagnoses were made for the family members seeking consultation based on the results of both clinical examination and genetic analysis.


RESULTS
Among three allelic variants identified in this pedigree (Pro13Leu [38 C-->T], Arg76Lys [227G-->A], and Gln337Stop [1009C del]), Pro13Leu and Gln337Stop were reported to be novel mutations while Arg76Lys has been previously documented. Our results show that all 11 POAG patients carry the Gln337Stop mutation and that four POAG patients and one POAG suspect (V:2) were found to have the Pro13Leu mutation. In addition, Arg76Lys polymorphism was identified in two patients and a POAG suspect (V:5).


CONCLUSIONS
Pro13Leu and Gln337Stop mutations of MYOC are likely responsible for the etiology of POAG in this pedigree, but the causative mechanism needs further research.
Xie
Xiaobing
X
Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, China.
Zhou
Xin
X
Qu
Xiying
X
Wen
Jing
J
Tian
Yanli
Y
Zheng
Fang
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000503:physiopathology; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics; D009154:Mutation / Q000187:drug effects*; D010375:Pedigree; D010641:Phenotype; D017433:Protein Structure, Secondary; D014794:Visual Fields / Q000502:physiology; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D050505:Mutant Proteins; D000099179:Myocilin
Hum Genet. 2004 Oct;115(5):428-31
15338275
Protein Eng. 1987 Aug-Sep;1(4):289-94
3508279
Mol Vis. 2004 Nov 09;10:851-6
15547491
Mol Vis. 2005 Apr 18;11:284-7
15851979
Am J Hum Genet. 1998 Nov;63(5):1549-52
9792882
Eye (Lond). 2000 Jun;14 ( Pt 3B):429-36
11026970
N Engl J Med. 1998 Apr 9;338(15):1022-7
9535666
J Mol Biol. 1978 Mar 25;120(1):97-120
642007
Arch Ophthalmol. 2000 Aug;118(8):1105-11
10922206
Hum Mol Genet. 1997 Nov;6(12):2091-7
9328473
Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3231-5
12356829
Mol Vis. 2002 Nov 15;8:442-8
12447164
Ophthalmic Genet. 2003 Jun;24(2):103-10
12789574
Hum Mol Genet. 2002 Sep 1;11(18):2077-90
12189160
Chin Med J (Engl). 2004 May;117(5):706-10
15161538
Invest Ophthalmol Vis Sci. 2006 Feb;47(2):620-5
16431959
Protein Eng. 1996 Feb;9(2):133-42
9005434
Exp Eye Res. 2006 Jun;82(6):1017-29
16466712
Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R91-102
14764620
Ophthalmic Genet. 2000 Jun;21(2):109-15
10916185
Invest Ophthalmol Vis Sci. 2000 May;41(6):1386-91
10798654
Hum Mol Genet. 1999 May;8(5):899-905
10196380
J Biol Chem. 2005 Jun 3;280(22):21043-51
15795224