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MERTK mutation update in inherited retinal diseases
Author(s) -
Audo Isabelle,
MohandSaid Saddek,
BoulangerScemama Elise,
Zanlonghi Xavier,
Condroyer Christel,
Démontant Vanessa,
Boyard Fiona,
Antonio Aline,
Méjécase Cécile,
El Shamieh Said,
Sahel JoséAlain,
Zeitz Christina
Publication year - 2018
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23431
Subject(s) - mertk , biology , missense mutation , genetics , dystrophy , retinal pigment epithelium , retinitis pigmentosa , retinal , phenotype , gene , receptor tyrosine kinase , kinase , biochemistry
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, 2 small insertion–deletions, 3 small duplications, and 2 exonic and 3 gross deletions. Altogether, mutations in MERTK account for ∼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.