目的探讨一个中国人原发性开角型青光眼（primary open angle glaucoma,POAG）家系的my-ocilin基因缺陷。方法对一个5代POAG大家系进行全面的临床检查后,用聚合酶链反应扩增家系成员myocilin基因的所有外显子以及相邻部分内含子,对其产...目的探讨一个中国人原发性开角型青光眼（primary open angle glaucoma,POAG）家系的my-ocilin基因缺陷。方法对一个5代POAG大家系进行全面的临床检查后,用聚合酶链反应扩增家系成员myocilin基因的所有外显子以及相邻部分内含子,对其产物直接测序。结果家系的遗传方式符合常染色体显性遗传。确诊年龄在26～59岁之间。在所有青光眼患者,可疑者以及4例尚未出现明显青光眼体征的家系成员发现携带myocilin基因T455K突变。无该突变的家系成员中无POAG患者及可疑者。突变位于myocilin蛋白C-末端非常保守的氨基酸残基。结论T455K突变是中国人所特有的新的致病性myocilin基因突变。突变的临床表型为混合发病年龄型POAG且具有很高的外显率。这个新基因突变的发现证实中国人的致病性myocilin基因突变类型与其他种族不同。展开更多
目的对原发性开角型青光眼(primary open angle glaucoma, POAG)患者的MYOC基因进行变异分析,探讨MYOC基因变异在散发型POAG发病中的作用。方法应用Sanger测序法对398例散发POAG患者的MYOC基因进行变异分析。结果在398例POAG患者的8例...目的对原发性开角型青光眼(primary open angle glaucoma, POAG)患者的MYOC基因进行变异分析,探讨MYOC基因变异在散发型POAG发病中的作用。方法应用Sanger测序法对398例散发POAG患者的MYOC基因进行变异分析。结果在398例POAG患者的8例中检出了5种MYOC基因的变异位点,其中c.667C>T(p.Pro223Ser)、c.1138G>T(p.Asp380Tyr)为未报道过的新变异位点,c.382C>T(p.Arg128Trp)、c.1109C>T(p.Pro370Leu)、c.1130C>A(p.Thr377Lys)为已报道的变异位点,与POAG发病相关。MYOC基因变异位点的检出率为2.0%(8/398)。多物种间氨基酸序列分析表明,2个新变异位点均位于高度保守区域。根据ACMG致病性标准分类和功能预测软件分析,推测MYOC基因c.1138G>T变异为可能致病性变异,c.667C>T变异位点的致病意义尚不明确。结论在散发POAG患者中检出了MYOC基因的2个新变异位点,丰富了MYOC基因的变异谱。展开更多
目的:观察对一原发性开角型青光眼(primar y open-angle glaucoma,POAG)家系的临床特点并筛查致病基因突变。方法:对先证者进行系统的临床检查,包括视力、眼压、裂隙灯、前房角镜、眼底、光学相干断层成像及视野检查。应用全外显子测序...目的:观察对一原发性开角型青光眼(primar y open-angle glaucoma,POAG)家系的临床特点并筛查致病基因突变。方法:对先证者进行系统的临床检查,包括视力、眼压、裂隙灯、前房角镜、眼底、光学相干断层成像及视野检查。应用全外显子测序技术对先证者进行致病基因筛查,结合临床表型,锁定候选基因致病突变位点,应用Sanger测序技术对先证者及其家系成员进行致病突变验证。结果:该家系4代共18人,为常染色体显性遗传方式,临床表型为POAG,其中POAG患者共8人(男3人,女5人)。先证者携带肌纤蛋白基因(MYOC)-c.754G>A(p.Gly252Arg)杂合错意突变,而另外2个非患病家系成员(先证者之兄及先证者女儿)未发现该突变。结论:通过对患者致病基因筛查,发现该POAG家系患病可能是由MYOC-c.754G>A(p.Gly252Arg)基因突变引起。MYOC Gly252Arg目前被认为与青少年起病的POAG表型相关,该基因突变在国内POAG家系遗传研究中尚未见报道。展开更多
Background: Glaucoma is the leading cause of irreversible blindness incapacitating over 80 million people worldwide. Several pathogenetic mechanisms have been postulated to explain the optic nerve damage that occur in...Background: Glaucoma is the leading cause of irreversible blindness incapacitating over 80 million people worldwide. Several pathogenetic mechanisms have been postulated to explain the optic nerve damage that occur in POAG among which genetic predisposition is prominent. Gene-Linkage-based studies have identified genes associated with POAG: Myocilin, Optineurin, WDR36, Tank-Binding Kinase (TBK1) and APbb-2. Objective: To investigate the prevalence of myocilin gene mutation in adult-onset POAG patients and non-glaucoma subjects who are indigenes of Rivers State. Methodology: In this comparative cross-sectional study, 393 POAG patients attending the Glaucoma Clinic of UPTH were compared with 393 age and sex-matched phenotypically normal participants. Clinical assessment combined with findings from clinical records was used. Venous blood was obtained for genomic analyses. Extracted DNA was sequenced with specific primers for myocilin and polymerase chain reaction. Zymo-Bead Genomic DNA kit protocol was used to detect allelic differences. Results: Total of 786 participants participated in the study. The mean age was 59.8 ± 11.8 years. The prevalence of myocilin gene mutation (MYOC) in the study population was 5.3%, in the POAG group was 8.4%, and 2.3% in the non-glaucoma group. This observed difference was statistically significant (p = 0.001). Location of the mutant myocilin gene was in GLC1A 171638779, 171638703, 171638610 and 171638608. Conclusion: Mutations in myocilin gene are associated with adult-onset POAG in Rivers State. Its relevance as a biomarker for diagnosis of adult-onset POAG needs further investigations.展开更多
文摘目的探讨一个中国人原发性开角型青光眼（primary open angle glaucoma,POAG）家系的my-ocilin基因缺陷。方法对一个5代POAG大家系进行全面的临床检查后,用聚合酶链反应扩增家系成员myocilin基因的所有外显子以及相邻部分内含子,对其产物直接测序。结果家系的遗传方式符合常染色体显性遗传。确诊年龄在26～59岁之间。在所有青光眼患者,可疑者以及4例尚未出现明显青光眼体征的家系成员发现携带myocilin基因T455K突变。无该突变的家系成员中无POAG患者及可疑者。突变位于myocilin蛋白C-末端非常保守的氨基酸残基。结论T455K突变是中国人所特有的新的致病性myocilin基因突变。突变的临床表型为混合发病年龄型POAG且具有很高的外显率。这个新基因突变的发现证实中国人的致病性myocilin基因突变类型与其他种族不同。
文摘目的对原发性开角型青光眼(primary open angle glaucoma, POAG)患者的MYOC基因进行变异分析,探讨MYOC基因变异在散发型POAG发病中的作用。方法应用Sanger测序法对398例散发POAG患者的MYOC基因进行变异分析。结果在398例POAG患者的8例中检出了5种MYOC基因的变异位点,其中c.667C>T(p.Pro223Ser)、c.1138G>T(p.Asp380Tyr)为未报道过的新变异位点,c.382C>T(p.Arg128Trp)、c.1109C>T(p.Pro370Leu)、c.1130C>A(p.Thr377Lys)为已报道的变异位点,与POAG发病相关。MYOC基因变异位点的检出率为2.0%(8/398)。多物种间氨基酸序列分析表明,2个新变异位点均位于高度保守区域。根据ACMG致病性标准分类和功能预测软件分析,推测MYOC基因c.1138G>T变异为可能致病性变异,c.667C>T变异位点的致病意义尚不明确。结论在散发POAG患者中检出了MYOC基因的2个新变异位点,丰富了MYOC基因的变异谱。
文摘目的:观察对一原发性开角型青光眼(primar y open-angle glaucoma,POAG)家系的临床特点并筛查致病基因突变。方法:对先证者进行系统的临床检查,包括视力、眼压、裂隙灯、前房角镜、眼底、光学相干断层成像及视野检查。应用全外显子测序技术对先证者进行致病基因筛查,结合临床表型,锁定候选基因致病突变位点,应用Sanger测序技术对先证者及其家系成员进行致病突变验证。结果:该家系4代共18人,为常染色体显性遗传方式,临床表型为POAG,其中POAG患者共8人(男3人,女5人)。先证者携带肌纤蛋白基因(MYOC)-c.754G>A(p.Gly252Arg)杂合错意突变,而另外2个非患病家系成员(先证者之兄及先证者女儿)未发现该突变。结论:通过对患者致病基因筛查,发现该POAG家系患病可能是由MYOC-c.754G>A(p.Gly252Arg)基因突变引起。MYOC Gly252Arg目前被认为与青少年起病的POAG表型相关,该基因突变在国内POAG家系遗传研究中尚未见报道。
文摘Background: Glaucoma is the leading cause of irreversible blindness incapacitating over 80 million people worldwide. Several pathogenetic mechanisms have been postulated to explain the optic nerve damage that occur in POAG among which genetic predisposition is prominent. Gene-Linkage-based studies have identified genes associated with POAG: Myocilin, Optineurin, WDR36, Tank-Binding Kinase (TBK1) and APbb-2. Objective: To investigate the prevalence of myocilin gene mutation in adult-onset POAG patients and non-glaucoma subjects who are indigenes of Rivers State. Methodology: In this comparative cross-sectional study, 393 POAG patients attending the Glaucoma Clinic of UPTH were compared with 393 age and sex-matched phenotypically normal participants. Clinical assessment combined with findings from clinical records was used. Venous blood was obtained for genomic analyses. Extracted DNA was sequenced with specific primers for myocilin and polymerase chain reaction. Zymo-Bead Genomic DNA kit protocol was used to detect allelic differences. Results: Total of 786 participants participated in the study. The mean age was 59.8 ± 11.8 years. The prevalence of myocilin gene mutation (MYOC) in the study population was 5.3%, in the POAG group was 8.4%, and 2.3% in the non-glaucoma group. This observed difference was statistically significant (p = 0.001). Location of the mutant myocilin gene was in GLC1A 171638779, 171638703, 171638610 and 171638608. Conclusion: Mutations in myocilin gene are associated with adult-onset POAG in Rivers State. Its relevance as a biomarker for diagnosis of adult-onset POAG needs further investigations.
