Humans ; Pharmacogenetics ; Precision Medicine ; Glaucoma/genetics*

OBJECTIVE: To screen for MYOC gene variants among sporadic patients with primary open angle glaucoma (POAG). METHODS: For 398 patients with POAG, Sanger sequencing was applied to detect potential variants of the MYOC gene. RESULTS: Eight patients (2.0%) were found to harbor variations of the MYOC gene. These included five types of variants, among which c.667C>T (p.Pro223Ser) and c.1138G>T (p.Asp380Tyr) were novel. c.382C>T (p.Arg128Trp), c.1109C>T(p.Pro370Leu) and c.1130C>A (p.Thr377Lys) were previously associated with POAG. Alignment of amino acid sequences of MYOC proteins of various species revealed that the two novel variants have occurred at highly conserved positions. c.1138G>T was predicted to be possible pathogenic by Bioinformatic analysis. CONCLUSION Two novel variants of the MYOC gene were detected among sporadic POAG patients, which enriched its variant spectrum.
Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Glaucoma, Open-Angle ; genetics ; Glycoproteins ; genetics ; Humans ; Mutation

Primary congenital glaucoma (PCG) is one of the major diseases causing blindness in children, but its pathogenesis has remained unclear. Genetic factors play an important role in the pathogenesis of PCG. Molecular genetics of candidate genes such as CYP1B1, MYOC, LTBP2 and FOXC1 has so far been explored, but no disease-causing gene has been identified. Molecular genetic research on PCG including candidate gene screening and research strategies are reviewed here.
Animals ; DNA Mutational Analysis ; Genetic Testing ; Glaucoma ; genetics ; Humans

BACKGROUNDGlaucoma is one of the leading causes of blindness in the world. Primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) are subtypes of glaucoma. Myocillin is the first gene identified to be involved in POAG. Recently, myocillin mutation has been found in PCG. In this context, we reported a special glaucoma pedigree, which was composed of both PCG and POAG patients, and analyzed the mutation of myocillin in this pedigree.

METHODSThe family was composed of the parents, a son and a daughter. All members of the family underwent the complete ophthalmologic examinations. All coding exons 1 - 3 and flanking introns of myocilin gene were screened for sequence alterations by polymerase chain reaction and direct DNA sequencing.

RESULTSThe son was the proband, who was diagnosed as PCG in both eyes. The father was diagnosed as POAG in the right eye, the left eye was still normal. Both the sister and the mother of the proband had normal intraocular pressure without glaucomatous optic disc changes. The mutations in intron 2 of myocilin gene were detected in the family. While the proband and the father were homozygous, the mother and the sister were heterozygous for the mutation.

CONCLUSIONSHomozygous mutation in intron 2 of myocilin gene is involved in both POAG and PCG. It is suggested that the pathogenesis might be overlapping in POAG and PCG.

Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Female ; Glaucoma ; congenital ; genetics ; Glaucoma, Open-Angle ; genetics ; Glycoproteins ; genetics ; Humans ; Introns ; Male ; Mutation ; Pedigree

Cataract ; genetics ; Diabetic Retinopathy ; genetics ; Eye Diseases ; genetics ; therapy ; Genetic Therapy ; Glaucoma, Open-Angle ; genetics ; Humans ; Macular Degeneration ; genetics

OBJECTIVETo assess the association of single nucleotide polymorphisms (SNPs) of PLEKHA7, COL11A1 and PCMTD1-ST18 genes and primary angle closure glaucoma (PACG) among ethnic Han Chinese from Sichuan Province.

METHODSIn this study, 362 subjects with PACG and 1056 age- and sex-matched healthy controls were recruited. Genotypes of 3 reported SNPs, including PLEKHA7 rs11024102, COL11A1 rs3753841 and PCMTD1-ST18 rs1015213 were determined with a SNaPshot method.

RESULTSThe P values for the genotype frequencies of rs11024102, rs3753841 and rs1015213 between the patient and control groups were 0.62 (OR=1.09, 95%CI: 0.91-1.30), 0.42 (OR=1.04, 95%CI: 0.87-1.41) and 0.34 (OR=1.35, 95%CI: 0.73-2.49), respectively. And the P values for the allele frequency distributions of PLEKHA7 rs11024102, COL11A1 rs3753841 and PCMTD1-ST18 rs1015213 between the two groups were 0.347, 0.698 and 0.344, respectively.

CONCLUSIONNo significant association of PLEKHA7 rs11024102, COL11A1 rs3753841 and PCMTD1-ST18 rs1015213 with PACG was found among ethnic Han Chinese from Sichuan.

Carrier Proteins ; genetics ; China ; ethnology ; Collagen Type XI ; genetics ; Female ; Glaucoma, Angle-Closure ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide ; Protein D-Aspartate-L-Isoaspartate Methyltransferase ; genetics

OBJECTIVETo investigate association between the lysyl oxidase-like 1 (LOXL1) gene single nucleotide polymorphism (SNP) and primary open-angle glaucoma (POAG) in Sichuan population.

METHODSIn this study,416 subjects with primary open-angle glaucoma and 997 normal controls were recruited.Three reported LOXL1 tag SNPs (rs1048661,rs3825942 and rs2165241) were genotyped by SNaPshot method.

RESULTSThe study showed that the genotypes of LOXL1 rs1048661,rs3825942 and rs2165241 between POAG and control groups were not statistically significant (OR=1.085, 95%CI 0.92-1.28, P=0.578 for rs1048661; OR=1.059, 95%CI 0.82-1.37, P=0.846 for rs3825942; OR=1.006, 95%CI 0.77-1.32, P=0.966 for rs2165241, respectively). There were no significant difference in allele frequency distribution of LOXL1 rs1048661、rs3825942 and rs2165241 between POAG and normal controls (P=0.322, P=0.660, P=0.965).

CONCLUSIONThe results from the present study do not indicate the association of LOXL1 SNPs (rs1048661, rs3825942 and rs2165241) with POAG in Sichuan population.

Adult ; Aged ; Aged, 80 and over ; Amino Acid Oxidoreductases ; genetics ; Asian Continental Ancestry Group ; genetics ; Glaucoma, Open-Angle ; genetics ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide

To elucidate the family history of glaucoma (FHG) as a risk factor for ocular hypertension(OH) vs glaucomatous optic nerve damage, we reviewed the clinical records of 361 primary open-angle glaucoma(POAG) patients, 178 OH subjects, and 927 normal controls randomly selected from an urban medical center eye clinic. The prevalence of a positive FHG was 27% in the POAG patients, 47% in the OH subjects, and 11% in the normal controls. Whereas a positive FHG was a significant risk factor for both OH and glaucoma compared to normal control subjects (OR = 7.56, 95% CI: 5.27-10.85, P < .0001 for OH; OR = 3.15, 95% CI: 2.31-4.31, P < .0001), it was a risk factor more significantly for OH than for glaucoma being significantly more prevalent in OH than in POAG (OR = 2.40, 95% CI: 1.65-3.49, P < .0001). These results suggest the importance of additional risk factors other than IOP for glaucomatous optic nerve damage.
Aged ; Family Health ; Female ; Glaucoma, Open-Angle/epidemiology/*genetics ; Humans ; *Intraocular Pressure ; Male ; Ocular Hypertension/epidemiology/*genetics ; Optic Nerve Diseases/epidemiology/*genetics ; Prevalence ; Questionnaires ; Random Allocation ; Risk Factors

BACKGROUNDGlaucoma is a major cause of irreversible blindness worldwide. There is evidence showing that a subset of the disease is genetically determined. In this study, we screened for mutations in chromosome 1q-linked open-angle glaucoma (GLC1A) in a Chinese family with primary open-angle glaucoma (POAG).

METHODSA total of 23 members from five generations of a family were enrolled and underwent thorough ophthalmologic examinations. In addition, 200 unrelated healthy Chinese controls were also recruited as normal control. GLC1A gene was amplified by polymerase chain reaction, and DNA sequencing was performed to screen for mutations.

RESULTSSix members were diagnosed as POAG, with severe clinical manifestations, and history of high intraocular pressures. The mean age of disease onset was 26.3 years. However, the others were asymptomatic. In six affected and three asymptomatic members, gene sequencing revealed a mutation c.C1456T in exon 3 of myocilin gene (MYOC). Furthermore, we also identified a novel mutation c.G322A in beta-1,4-galactosyltransferase 3 (B4GALT3) gene in all six affected and three asymptomatic members, which was not reported previously in POAG patients. The two newly identified variants were absent in other family members as well as controls.

CONCLUSIONThe mutations c.1456C < T (p.L486F) in MYOC and c.322G < A (p.V108I) in B4GALT3 are likely responsible for the pathogenesis of POAG in this family.

Adult ; Computational Biology ; Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Genetic Testing ; Glaucoma, Open-Angle ; genetics ; Glycoproteins ; genetics ; Humans ; Male ; Mutation ; genetics ; N-Acetyllactosamine Synthase ; genetics ; Pedigree ; Sequence Analysis, DNA ; Young Adult

OBJECTIVETo describe the clinical and genetic characteristics of a Chinese family with primary angle-closure glaucoma (PACG).

METHODSLinkage analysis and DNA sequencing as well as single strand conformation polymorphism (SSCP) analysis were performed to identify the disease-causing mutations.

RESULTSThe Arg46Stop mutation in MYOC gene and Leu432Val in CYP1B1 gene were identified in all patients. The digenic alterations have not been identified in any same Chinese control individuals.

CONCLUSIONAuthor identified digenic mutations, Arg46Stop in MYOC gene and Leu432Val in CYP1B1 gene, in a Chinese PACG family. Author's studies suggest a possible role of MYOC and CYP1B1 in the development of PACG and support the hypothesis that PAOG and PACG may have common origin across multiple glaucoma phenotypes.

Aged ; Alleles ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Cytochrome P-450 CYP1B1 ; Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Female ; Genotype ; Glaucoma, Angle-Closure ; genetics ; Glycoproteins ; genetics ; Humans ; Mutation ; Pedigree ; Phenotype ; Polymorphism, Genetic