Wirtz Mary K, Samples John R, Choi Dongseok, Gaudette N Donna
Casey Eye Institute, Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon 97239, USA.
Am J Ophthalmol. 2007 Jul;144(1):75-80. doi: 10.1016/j.ajo.2007.03.037. Epub 2007 May 11.
To determine the glaucoma phenotype of an American pedigree with the myocilin Asp380His.
An observational case series study.
An observational case series study was used to examine a family in which an Asp380His myocilin mutation was segregating. Thirteen family members were examined and medical records were obtained on the remaining two individuals. Blood samples were collected from all 15 participants following the tenets of the Helsinki declaration under the auspices of the Oregon Health & Sciences University Institutional Review Board and screened for myocilin variants by denaturing high-performance liquid chromatography (dHPLC). Any DNA samples with dHPLC data different from the control sample were sequenced for base pair analysis.
An Asp380His myocilin mutation was identified in eight members, seven of whom had primary open-angle glaucoma (POAG). The eighth individual had high intraocular pressures (IOPs). The disease presents in this family with extremely high IOPs requiring trabeculectomies to control the pressure. The age at diagnosis ranged from 30 to 45.
This family with an Asp380His myocilin mutation presents with an intermediate phenotype between juvenile- and adult-onset glaucoma. The Asp380 amino acid residue appears to be important in myocilin function based on the finding that substitution of this amino acid with four different amino acids (His, Ala, Asn, or Gly) all result in a similar presentation of POAG that is intermediate between the more severe clinical presentations observed in individuals with the Pro370Leu or Lys423Glu variant and the milder findings in patients with the Gln368Stop mutation.
确定携带肌纤蛋白Asp380His突变的一个美国家系的青光眼表型。
一项观察性病例系列研究。
采用观察性病例系列研究来检查一个肌纤蛋白Asp380His突变呈分离状态的家族。对13名家族成员进行了检查，并获取了其余两名个体的医疗记录。在俄勒冈健康与科学大学机构审查委员会的主持下，按照赫尔辛基宣言的原则，从所有15名参与者身上采集了血样，并通过变性高效液相色谱法（dHPLC）筛查肌纤蛋白变体。对任何dHPLC数据与对照样品不同的DNA样本进行测序以进行碱基对分析。
在8名成员中鉴定出肌纤蛋白Asp380His突变，其中7人患有原发性开角型青光眼（POAG）。第八名个体眼压升高。该疾病在这个家族中表现为眼压极高，需要进行小梁切除术来控制眼压。诊断年龄在30至45岁之间。
这个携带肌纤蛋白Asp380His突变的家族呈现出青少年型和成人型青光眼之间的中间表型。基于以下发现，即该氨基酸被四种不同氨基酸（His、Ala、Asn或Gly）取代均导致POAG的类似表现，这种表现介于携带Pro370Leu或Lys423Glu变体的个体中观察到的更严重临床表现与携带Gln368Stop突变的患者中较轻表现之间，Asp380氨基酸残基似乎在肌纤蛋白功能中很重要。
