五例成人型卵黄样黄斑营养不良患者临床表型特征及致病基因突变分析  

Gene mutations and clinical features of adult vitelliform macular dystrophy in 5 patients

作　　者：薛莹[1] 张勇进[1] 王敏[1] 刘卫[1] 徐格致[1] 

机构地区：[1]复旦大学附属眼耳鼻喉科医院眼科,上海200031

出　　处：《中华眼科杂志》2014年第7期523-528,共6页Chinese Journal of Ophthalmology

基　　金：上海市自然科学基金（12ZR1404800）

摘　　要：目的 探讨成人型卵黄样黄斑营养不良（AVMD）患者临床表型特征和相关致病基因突变特点.方法 病例对照研究.对2012年1至12月在复旦大学附属眼耳鼻喉科医院眼科就诊的5例AVMD患者进行详尽的眼科检查及Best1和peripherin/RDS基因突变筛查.采用相同方法对50名对照者进行筛查以便比较.结果 5例患者平均发病年龄为45岁（28～59岁）.2例为双眼发病,3例为单眼发病,其中1例患者对侧眼黄斑萎缩.基因筛查在1例患者检测出一个新的peripherin/RDS基因突变：第3号外显子1009位碱基G-A替换（1009 G＞A）,导致氨基酸序列发生改变,同时伴有轻度的眼电图（EOG）异常.在对照组中并未发现上述情况.结论 与peripherin/RDS基因突变相关联的AVMD具有自身特殊的临床表现.位于peripherin/RDS基因C-末端的突变可能在疾病的发生发展中起到关键作用,AVMD的临床表型与基因型之间存在一定的关联性.Objective To describe the clinical features as well as mutations in 2 relative genes in 5 cases with macular dystrophies presenting with vitelliform lesions in adulthood.Methods Case control study.A total of 5 patients visited Eye and ENT Hospital of Fudan University between January and December 2012 and diagnosed with adult onset macular dystrophy were reviewed.Patient evaluation included complete ophthalmic examinations,such as optical coherence tomography,fundus photography,electrooculogram testing and fundus autofluorescence.The Best1 and peripherin/RDS genes were screened for variation by direct DNA sequencing of coding regions and intron/exon boundaries.At the same time,50 controls were screened in the same way to get comparisons.Results The age at the time of diagnosis ranged from 28 to 59 years with the average of 45 years.2 patients were affected bilaterally,while the other 3 were unilateral Attack.Moreover,vitelliform lesion and macular atrophy was found in 2 eyes separately in 1 patient.Direct sequencing of PCR products spanning all exons revealed a noval missense mutation in 1 patient：1009 G 〉 A,causing a Ala 337 Thr change in Peripherin/RDS gene exon 3,as well as a slightly reduced EOG Arden index bilaterally.There was no such change in controls.Conclusions The AVMD related with mutations in peripherin/RDS gene has its own clinical features.The mutation near the C-terminal domain of the polypeptide may play a crucial role in the development of AVMD.There is some relevance between clinical feature and genetype in AVMD.

关 键 词：卵黄样黄斑营养不良 视网膜疾病 DNA突变分析 表型 

分 类 号：R774.5[医药卫生—眼科]