ABCA4 gene sequence variations in patients with autosomal recessive cone-rod dystrophy
ABCA4 gene sequence variations in patients with autosomal recessive cone-rod dystrophy
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DOI：
10.1001/archopht.121.6.851
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发表时间：
2003-06-01
影响因子：
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通讯作者：
Derlacki, DJ
中科院分区：
文献类型：
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作者：
Fishman, GA;Stone, EM;Derlacki, DJ
目的：为了确定ABCA 4基因的序列变异在一个队列的患者与常染色体隐性视锥-视杆细胞营养不良。方法：ABCA 4基因的编码序列进行了分析，在30个无关的先证者。在这些患者与合理的致病变异，基因型和眼底表型之间的相关性，以及与电生理和视野findings.Results：十六（53%）的30个先证者被发现窝藏合理的致病变异的ABCA 4基因。在我们的患者队列中观察到两种明显不同的眼底表型。12例患者表现为弥漫性色素变性改变，而4例患者表现为无色素变性或仅轻度外周色素变性。一定的序列变异和这两个不同的phenotypesobserved.Conclusions之间的关联：我们的研究结果证实，相当大比例的常染色体隐性遗传性视锥杆细胞营养不良的患者很可能窝藏在ABCA 4基因突变的原因，他们的疾病。在这些患者中观察到的眼底表型是相当可变的，某些眼底表型可能与某些genotype.Clinical Relevance：各种遗传性人类视网膜营养不良，如锥-杆营养不良的分子遗传基础的鉴定，促进了潜在的更好地了解感光细胞退化的机制。这反过来又为如何更好地确定最佳的未来治疗策略提供了指导。
Objective: To identify sequence variations in the ABCA4 gene in a cohort of patients with autosomal recessive cone-rod dystrophy.Methods: The coding sequences of the ABCA4 gene were analyzed in 30 unrelated probands. In those patients with plausible disease-causing variations, correlations were made between genotype and fundus phenotype as well as with electrophysiological and visual field findings.Results: Sixteen (53%) of 30 probands were found to harbor plausible disease-causing variations in the ABCA4 gene. Two distinctly different fundus phenotypes were observed in our cohort of patients. Twelve patients showed diffuse pigmentary degenerative changes, whereas 4 showed either no pigmentary changes or only a mild degree of peripheral pigment degeneration. An association between certain sequence variations and each of these 2 different phenotypes was observed.Conclusions: Our findings confirm that a substantial percentage of patients with autosomal recessive cone-rod dystrophy are likely to harbor a mutation in the ABCA4 gene as the cause of their disease. The fundus phenotype observed in such patients is quite variable, and certain fundus phenotypes may be more associated with certain genotypes.Clinical Relevance: Identification of the molecular genetic basis for various inherited human retinal dystrophies, such as cone-rod dystrophy, facilitates a potentially better understanding of the mechanisms by which photoreceptor cells degenerate. This in turn provides guidance as to how to better proceed in identifying the most optimal future therapeutic strategies.