Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset open angle glaucoma.
OBJECTIVE
To describe the clinical and genetic findings in one Chinese family with juvenile-onset open angle glaucoma (JOAG).


METHODS
One family was examined clinically and a follow-up took place 5 years later. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Linkage analysis was performed with three microsatellite markers around the MYOC gene (D1S196, D1S2815, and D1S218) in the family. Mutation screening of all coding exons of MYOC was performed by direct sequencing of PCR-amplified DNA fragments and restriction fragment length polymorphism (RFLP) analysis. Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted the effects of variants detected on secondary structures of the MYOC protein.


RESULTS
Clinical examination and pedigree analysis revealed a three- generation family with seven members diagnosed with JOAG, three with ocular hypertension, and five normal individuals. Through genotyping, the pedigree showed a linkage to the MYOC on chromosome 1q24-25. Mutation screening of MYOC in this family revealed an A-->T transition at position 1348 (p. N450Y) of the cDNA sequence. This missense mutation co-segregated with the disease phenotype of the family, but was not found in 100 normal controls. Secondary structure prediction of the p.N450Y by the GOR method revealed the replacement of a coil with a beta sheet at the amino acid 447.


CONCLUSIONS
Early onset JOAG, with incomplete penetrance, is consistent with a novel mutation in MYOC. The finding provides pre-symptomatic molecular diagnosis for the members of this family and is useful for further genetic consultation.
Zhao
Xin
X
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.
Yang
Chaoshan
C
Tong
Yi
Y
Zhang
Xiaohui
X
Xu
Liang
L
Li
Yang
Y
D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China / Q000453:epidemiology; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005190:Family; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000453:epidemiology* / Q000235:genetics*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017433:Protein Structure, Secondary; D055815:Young Adult; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin
Nat Genet. 1993 May;4(1):47-50
8513321
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Dec;24(6):629-34
18067072
Am J Hum Genet. 2002 Feb;70(2):448-60
11774072
Mol Vis. 2009 Sep 24;15:1945-50
19784393
Surv Ophthalmol. 2002 Nov-Dec;47(6):547-61
12504739
Science. 2002 Feb 8;295(5557):1077-9
11834836
Arch Ophthalmol. 2000 May;118(5):674-9
10815160
Am J Ophthalmol. 2000 Aug;130(2):165-77
11004290
Mol Vis. 2005 Aug 29;11:625-31
16148883
Mol Vis. 2008 Aug 22;14:1533-9
18728751
Am J Hum Genet. 1996 Jan;58(1):243-4
8554064
Mol Vis. 2008 Mar 04;14:413-7
18334962
Am J Hum Genet. 1998 Nov;63(5):1549-52
9792882
Mol Vis. 2008 Sep 05;14:1666-72
18776955
Am J Ophthalmol. 2007 Jul;144(1):75-80
17499207
Science. 1997 Jan 31;275(5300):668-70
9005853
Br J Ophthalmol. 1997 May;81(5):409-14
9227209
Mol Vis. 2006 Apr 17;12:360-6
16636654
Br J Ophthalmol. 2006 Mar;90(3):262-7
16488940
Arch Ophthalmol. 2006 Jan;124(1):102-6
16401791
Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R91-102
14764620
Am J Hum Genet. 1998 Mar;62(3):641-52
9497264
Hum Mol Genet. 2005 Mar 15;14(6):725-33
15677485
Hum Mutat. 2002 Dec;20(6):479-80
12442283
Mol Vis. 2007 Sep 27;13:1793-801
17960117
Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2288-95
9804137
Curr Opin Ophthalmol. 2000 Apr;11(2):101-6
10848214
Hum Mutat. 2008 Feb;29(2):207-11
17966125
Arch Ophthalmol. 2003 Jul;121(7):1034-8
12860809
Hum Mol Genet. 1997 Nov;6(12):2091-7
9328473
Yan Ke Xue Bao. 2007 Jun;23(2):75-8
17867509
Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3231-5
12356829
Methods Enzymol. 1996;266:540-53
8743705
Korean J Ophthalmol. 1997 Dec;11(2):75-8
9510647
Hum Mol Genet. 1999 May;8(5):899-905
10196380
Invest Ophthalmol Vis Sci. 2008 Jan;49(1):270-4
18172102