Fishman Gerald A, Stone Edwin M, Eliason David A, Taylor Chris M, Lindeman Martin, Derlacki Deborah J
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 60612, USA.
Arch Ophthalmol. 2003 Jun;121(6):851-5. doi: 10.1001/archopht.121.6.851.
To identify sequence variations in the ABCA4 gene in a cohort of patients with autosomal recessive cone-rod dystrophy.
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.
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 associa-tion between certain sequence variations and each of these 2 different phenotypes was observed.
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.
在一组常染色体隐性遗传的视锥视杆营养不良患者中鉴定ABCA4基因的序列变异。
对30名无亲缘关系的先证者的ABCA4基因编码序列进行分析。对于那些有合理致病变异的患者，分析基因型与眼底表型以及与电生理和视野检查结果之间的相关性。
30名先证者中有16名（53%）被发现携带ABCA4基因的合理致病变异。在我们的患者队列中观察到两种明显不同的眼底表型。12名患者表现为弥漫性色素性退行性改变，而4名患者要么没有色素性改变，要么只有轻度周边色素变性。观察到某些序列变异与这两种不同表型中的每一种之间存在关联。
我们的研究结果证实，相当比例的常染色体隐性遗传视锥视杆营养不良患者可能携带ABCA4基因突变作为其疾病病因。此类患者观察到的眼底表型差异很大，某些眼底表型可能与某些基因型更相关。临床意义 确定各种遗传性人类视网膜营养不良（如视锥视杆营养不良）的分子遗传基础，有助于更好地理解光感受器细胞退化的机制。这反过来又为如何更好地确定未来最优化的治疗策略提供指导。
