Abstract：
BACKGROUND: Waardenburg syndrome is an autosomal dominant disorder with varying degrees of sensorineural hearing loss as well as abnormal pigmentation in hair, skin, and iris. There are four types of Waardenburg syndrome (1-4) with different characteristics. Mutations in six genes have been identified to be associated with the various types. Herein, we describe a case of Waardenburg syndrome type 4 combined with open-angle glaucoma.
METHODS: A 43-year-old Han Chinese man had undergone trabeculectomy due to progression of visual field impairment and unstable intraocular pressure in both eyes. Slit-lamp examination revealed diffuse iris hypopigmentation in the left eye and hypopigmentation of part of the iris in the right eye. Fundus examination showed red, sunset-like fundus due to a lack of pigmentation in the retinal pigment epithelium layer, diffuse loss of the nerve fiber layer, and an excavated optic nerve head with advanced-stage glaucoma. Imaging was performed using anterior segment optical coherence tomography to detect the iris configuration. In the heterochromic iris portion, the normal part of the iris showed a clear hyperreflective signal of the anterior border layer, while atrophy of the pigmented anterior border layer showed a hyporeflective area of the anterior surface resulting in reduced light absorption. Two mutations of the endothelin receptor type B gene were recognized in this study. The first (c.1111G>A on exon 7) leads to an amino acid change from glycine to serine at codon 371. Sanger verification revealed that this mutation is inherited from the mother. The other mutation (c.553G>A) leads to an amino acid change from valine to methionine at codon 185. Sanger verification showed that this mutation was inherited from the father.
CONCLUSIONS: Waardenburg syndrome shows a remarkable diversity in clinical presentation and morphology. This disease can also present with open-angle glaucoma. Sequencing analysis revealed two heterozygous mutations in the EDNRB gene in this patient, inherited from his mother and father, respectively. These two sites constitute a compound heterozygous variation.
METHODS: A 43-year-old Han Chinese man had undergone trabeculectomy due to progression of visual field impairment and unstable intraocular pressure in both eyes. Slit-lamp examination revealed diffuse iris hypopigmentation in the left eye and hypopigmentation of part of the iris in the right eye. Fundus examination showed red, sunset-like fundus due to a lack of pigmentation in the retinal pigment epithelium layer, diffuse loss of the nerve fiber layer, and an excavated optic nerve head with advanced-stage glaucoma. Imaging was performed using anterior segment optical coherence tomography to detect the iris configuration. In the heterochromic iris portion, the normal part of the iris showed a clear hyperreflective signal of the anterior border layer, while atrophy of the pigmented anterior border layer showed a hyporeflective area of the anterior surface resulting in reduced light absorption. Two mutations of the endothelin receptor type B gene were recognized in this study. The first (c.1111G>A on exon 7) leads to an amino acid change from glycine to serine at codon 371. Sanger verification revealed that this mutation is inherited from the mother. The other mutation (c.553G>A) leads to an amino acid change from valine to methionine at codon 185. Sanger verification showed that this mutation was inherited from the father.
CONCLUSIONS: Waardenburg syndrome shows a remarkable diversity in clinical presentation and morphology. This disease can also present with open-angle glaucoma. Sequencing analysis revealed two heterozygous mutations in the EDNRB gene in this patient, inherited from his mother and father, respectively. These two sites constitute a compound heterozygous variation.
摘要：
背景：Waardenburg综合征是一种常染色体显性遗传性疾病，伴有不同程度的感觉神经性听力损失以及头发中的异常色素沉着，皮肤,还有虹膜.有四种类型的Waardenburg综合征（1-4）具有不同的特征。已经鉴定出六个基因中的突变与各种类型有关。在这里，我们描述了1例Waardenburg综合征4型合并开角型青光眼。
方法：一名43岁的汉族男性因视野损害进展和双眼眼压不稳定而接受了小梁切除术。裂隙灯检查显示左眼弥漫性虹膜色素减退，右眼部分虹膜色素减退。眼底检查显示红色，由于视网膜色素上皮层缺乏色素沉着，神经纤维层的弥漫性损失，和患有晚期青光眼的挖出的视神经头。使用眼前段光学相干断层扫描进行成像以检测虹膜配置。在异色虹膜部分，虹膜的正常部分显示出明显的前交界层的超反射信号，而色素沉着的前交界层的萎缩显示前表面的低反射区域，导致光吸收减少。在这项研究中，内皮素受体B型基因的两个突变被识别。第一个(外显子7上的c.1111G>A)导致密码子371处的氨基酸从甘氨酸变为丝氨酸。桑格验证表明，这种突变是从母亲那里遗传的。另一个突变(c.553G>A)导致在密码子185处从缬氨酸到甲硫氨酸的氨基酸改变。Sanger验证表明该突变是从父亲那里遗传的。
结论：Waardenburg综合征在临床表现和形态上表现出显著的多样性。这种疾病也可以表现为开角型青光眼。测序分析显示该患者的EDNRB基因有两个杂合突变，从他的母亲和父亲那里继承下来，分别。这两个位点构成复合杂合变异。
方法：一名43岁的汉族男性因视野损害进展和双眼眼压不稳定而接受了小梁切除术。裂隙灯检查显示左眼弥漫性虹膜色素减退，右眼部分虹膜色素减退。眼底检查显示红色，由于视网膜色素上皮层缺乏色素沉着，神经纤维层的弥漫性损失，和患有晚期青光眼的挖出的视神经头。使用眼前段光学相干断层扫描进行成像以检测虹膜配置。在异色虹膜部分，虹膜的正常部分显示出明显的前交界层的超反射信号，而色素沉着的前交界层的萎缩显示前表面的低反射区域，导致光吸收减少。在这项研究中，内皮素受体B型基因的两个突变被识别。第一个(外显子7上的c.1111G>A)导致密码子371处的氨基酸从甘氨酸变为丝氨酸。桑格验证表明，这种突变是从母亲那里遗传的。另一个突变(c.553G>A)导致在密码子185处从缬氨酸到甲硫氨酸的氨基酸改变。Sanger验证表明该突变是从父亲那里遗传的。
结论：Waardenburg综合征在临床表现和形态上表现出显著的多样性。这种疾病也可以表现为开角型青光眼。测序分析显示该患者的EDNRB基因有两个杂合突变，从他的母亲和父亲那里继承下来，分别。这两个位点构成复合杂合变异。
