MERTK mutation update in inherited retinal diseases

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.     

Cerebellar asymmetry,cortical asymmetry and handedness: Two independent networks

ABSTRACT

In 46 right-handers and 46 left-handers, we used functional magnetic resonance imaging to record activity in the frontal lobes while they generated words, the temporal lobe while they made synonym judgments, and the parietal lobe while they watched videos of manual actions. In each case we also recorded activity in the cerebellum. Laterality indices showed a significant left-hemispheric bias in each cortical lobe and a right-hemispheric bias in the cerebellum for the 2 language tasks, but not during action observation. Cerebellar asymmetry also correlated negatively with frontal and temporal asymmetry, reflecting contralateral connections, but not with parietal asymmetry. A factor analysis of the inter-correlations among laterality indices revealed 2 factors, implying independent lateralized networks, with cerebellar asymmetry strongly linked to a language network in frontal and temporal cortices, and handedness strongly linked to an action-observation network in the parietal lobe.