MERTK mutation update in inherited retinal diseases
MERTK mutation update in inherited retinal diseases
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DOI：
10.1002/humu.23431
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发表时间：
2018-07-01
期刊：
影响因子：
3.9
通讯作者：
Zeitz, Christina
中科院分区：
文献类型：
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作者：
Audo, Isabelle;Mohand-Said, Saddek;Zeitz, Christina
MER酪氨酸激酶（MERTK）编码位于视网膜色素上皮细胞顶膜的表面受体。它在吞噬前的感光细胞外节内化中起关键作用。在RCS大鼠和人类中，MERTK突变与重度常染色体隐性视网膜营养不良相关。我们在此对所有报告的MERTK致病变异体及其相关表型进行了全面综述。此外，我们还提供了1，195例遗传性视网膜营养不良（IRD）指数病例的大型队列的进一步数据和见解，这些病例采用了最先进的基因分型技术，并总结了当前的知识。现已确定总共79种变异是视杆-视锥营养不良和视锥-视杆营养不良的基础，其中包括本文报告的11种新型变异。MERTK中的突变谱包括33个错义、12个无义、12个剪接缺陷、12个小缺失、2个小插入缺失、3个小重复、2个外显子缺失和3个总缺失。总的来说，MERTK突变占具有严重视网膜表型的IRD病例的2%。这些数据对于当前和未来的治疗试验（包括基因替代疗法或基于细胞的疗法）非常重要。
MER tyrosine kinase (MERTK) encodes a surface receptor localized at the apical membrane of the retinal pigment epithelium. It plays a critical role in photoreceptor outer segment internalization prior to phagocytosis. Mutations in MERTK have been associated with severe autosomal recessive retinal dystrophies in the RCS rat and in humans. We present here a comprehensive review of all reported MERTK disease causing variants with the associated phenotype. In addition, we provide further data and insights of a large cohort of 1,195 inherited retinal dystrophies (IRD) index cases applying state-of-the-art genotyping techniques and summarize current knowledge. A total of 79 variants have now been identified underlying rod-cone dystrophy and cone-rod dystrophy including 11 novel variants reported here. The mutation spectrum in MERTK includes 33 missense, 12 nonsense, 12 splice defects, 12 small deletions, two small insertion-deletions, three small duplications, and two exonic and three gross deletions. Altogether, mutations in MERTK account for similar to 2% of IRD cases with a severe retinal phenotype. These data are important for current and future therapeutic trials including gene replacement therapy or cell-based therapy.