Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene
Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene
复制标题
DOI：
10.1001/archopht.117.4.504
复制
发表时间：
1999-04-01
影响因子：
--
通讯作者：
Hockey, RR
中科院分区：
文献类型：
--
作者：
Fishman, GA;Stone, EM;Hockey, RR
目的：报道具有特定ABCR基因序列变异的Stargardt营养不良或黄斑眼底病患者的眼科表现谱。患者：从66例患者中筛选出29例来自不同家系的Stargardt营养不良或黄斑眼底营养不良患者的ABCR基因可能致病的序列变异。对22例患者进行了荧光素血管造影，并对其中24例患者进行了视网膜电生理检查。用Goldmann视野计测量了26例患者的动态视野。用单链构象多态分析和DNA测序分析ABCR基因编码序列的变异。结果：29例患者有3种临床表型。在表型I型中，9例患者ABCR基因第42外显子发生序列改变，氨基酸谷氨酸取代甘氨酸(Gly1961Glu)。在这9名患者中，只有4名在其他ABCR等位基因上发现了第二种可能的致病突变。除了萎缩性黄斑病变外，表型I型的特点是黄斑周围有局限性的黄白色斑点，没有暗色脉络膜，视网膜电图波幅正常。表型II包括10名患者，他们的眼底有较深的脉络膜和弥漫的黄白色斑点。没有人表现出Gly1961Glu的变化。表型III7例，表现为视网膜色素上皮广泛萎缩样变。视网膜电图视锥和视杆细胞的波幅降低。1例患者表现出Gly1961Glu改变。结论：在ABCR基因序列改变的患者中，临床表型会发生很大的变化。在个别患者中，特定的表型似乎与ABCR基因第42外显子的Gly1961Glu变化有关。临床相关性：确定ABCR基因特定突变与临床表型之间的相关性将更有助于对患者的视力预后进行咨询。这一信息对Stargardt营养不良患者未来的治疗试验也可能是重要的。
Objective: To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene.Patients: Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene.Methods: Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene.Results: Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change.Conclusions: A wide variation in clinical phenotype can occur inpatients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene.Clinical Relevance: The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.