Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations.
Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations.
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DOI：
10.1016/j.preteyeres.2020.100861
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发表时间：
2020-11
影响因子：
17.8
通讯作者：
Allikmets R
中科院分区：
文献类型：
--
作者：
Cremers FPM;Lee W;Collin RWJ;Allikmets R
ABCA 4蛋白（当时称为“边缘蛋白”）于1978年首次在视杆细胞的边缘和切口中被鉴定。相应的基因ABCA 4于1997年被克隆，其变体被鉴定为常染色体隐性遗传性Stargardt病（STGD 1）的病因。在接下来的二十年中，ABCA 4的变化已归因于除经典定义的STGD 1或眼底黄斑症以外的表型，范围从早发和快速进展的视锥-视杆营养不良和视网膜色素变性样表型到非常晚发的大多数轻度疾病的病例，有时类似于年龄相关性黄斑变性并与之混淆。类似地，ABCA 4基因座的分析揭示了大量的遗传信息，包括>1200种不同严重程度的致病突变，以及所有类型的突变-错义、无义、小缺失/插入和影响剪接的变体，其中许多位于深内含子。总而言之，这大大扩展了我们对ABCA 4突变引起的疾病的复杂性的理解，但一般来说，所有孟德尔疾病。本综述提供了对ABCA 4相关视网膜病变的累积知识的深入评估-临床表现，遗传复杂性，病理生理学以及当前和拟议的治疗方法。
The ABCA4 protein (then called a “rim protein”) was first identified in 1978 in the rims and incisures of rod photoreceptors. The corresponding gene, ABCA4, was cloned in 1997, and variants were identified as the cause of autosomal recessive Stargardt disease (STGD1). Over the next two decades, variation in ABCA4 has been attributed to phenotypes other than the classically defined STGD1 or fundus flavimaculatus, ranging from early onset and fast progressing cone-rod dystrophy and retinitis pigmentosa-like phenotypes to very late onset cases of mostly mild disease sometimes resembling, and confused with, age-related macular degeneration. Similarly, analysis of the ABCA4 locus uncovered a trove of genetic information, including >1200 disease-causing mutations of varying severity, and of all types – missense, nonsense, small deletions/insertions, and splicing affecting variants, of which many are located deep-intronic. Altogether, this has greatly expanded our understanding of complexity not only of the diseases caused by ABCA4 mutations, but of all Mendelian diseases in general. This review provides an in depth assessment of the cumulative knowledge of ABCA4-associated retinopathy – clinical manifestations, genetic complexity, pathophysiology as well as current and proposed therapeutic approaches.
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影响因子：
4.4
作者：
Beit-Ya'acov, Anat;Mizrahi-Meissonnier, Liliana;Sharon, Dror
通讯作者：
Sharon, Dror
影响因子：
3.9
作者：
Bax, Nathalie M.;Sangermano, Riccardo;Cremers, Frans P. M.
通讯作者：
Cremers, Frans P. M.
DOI：
10.1097/iae.0000000000001716
发表时间：
2018-07
期刊：
Retina (Philadelphia, Pa.)
影响因子：
--
作者：
Arepalli S;Traboulsi EI;Ehlers JP
通讯作者：
Ehlers JP
影响因子：
3.4
作者：
Birch, DG;Peters, AY;Travis, GH
通讯作者：
Travis, GH
影响因子：
9.8
作者：
Albert, Silvia;Garanto, Alejandro;Cremers, Frans P. M.
通讯作者：
Cremers, Frans P. M.