@article{discovery1546386,
           pages = {592--604},
         journal = {American Journal of Human Genetics},
           month = {April},
            note = {Copyright {\copyright} 2017 American Society of Human Genetics. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)},
          number = {4},
           title = {Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies},
            year = {2017},
          volume = {100},
        keywords = {CRISPR-Cas9, CWC27, brachydachtyly, craniofacial defects, neurological defects, retinal degeneration, short stature, spliceosome, syndrome},
            issn = {1537-6605},
        abstract = {Pre-mRNA splicing factors play a fundamental role in regulating transcript diversity both temporally and spatially. Genetic defects in several spliceosome components have been linked to a set of non-overlapping spliceosomopathy phenotypes in humans, among which skeletal developmental defects and non-syndromic retinitis pigmentosa (RP) are frequent findings. Here we report that defects in spliceosome-associated protein CWC27 are associated with a spectrum of disease phenotypes ranging from isolated RP to severe syndromic forms. By whole-exome sequencing, recessive protein-truncating mutations in CWC27 were found in seven unrelated families that show a range of clinical phenotypes, including retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurological defects. Remarkably, variable expressivity of the human phenotype can be recapitulated in Cwc27 mutant mouse models, with significant embryonic lethality and severe phenotypes in the complete knockout mice while mice with a partial loss-of-function allele mimic the isolated retinal degeneration phenotype. Our study describes a retinal dystrophy-related phenotype spectrum as well as its genetic etiology and highlights the complexity of the spliceosomal gene network.},
             url = {http://dx.doi.org/10.1016/j.ajhg.2017.02.008},
          author = {Xu, M and Xie, YA and Abouzeid, H and Gordon, CT and Fiorentino, A and Sun, Z and Lehman, A and Osman, IS and Dharmat, R and Riveiro-Alvarez, R and Bapst-Wicht, L and Babino, D and Arno, G and Busetto, V and Zhao, L and Li, H and Lopez-Martinez, MA and Azevedo, LF and Hubert, L and Pontikos, N and Eblimit, A and Lorda-Sanchez, I and Kheir, V and Plagnol, V and Oufadem, M and Soens, ZT and Yang, L and Bole-Feysot, C and Pfundt, R and Allaman-Pillet, N and Nitschk{\'e}, P and Cheetham, ME and Lyonnet, S and Agrawal, SA and Li, H and Pinton, G and Michaelides, M and Besmond, C and Li, Y and Yuan, Z and von Lintig, J and Webster, AR and Le Hir, H and Stoilov, P and UK Inherited Retinal Dystrophy Consortium, . and Amiel, J and Hardcastle, AJ and Ayuso, C and Sui, R and Chen, R and Allikmets, R and Schorderet, DF}
}