@article {560,
	title = {Loss of tubulin deglutamylase CCP1 causes infantile-onset neurodegeneration.},
	journal = {EMBO J},
	volume = {37},
	year = {2018},
	month = {2018 Dec 03},
	abstract = {<p>A set of glutamylases and deglutamylases controls levels of tubulin polyglutamylation, a prominent post-translational modification of neuronal microtubules. Defective tubulin polyglutamylation was first linked to neurodegeneration in the  () mouse, which lacks deglutamylase CCP1, displays massive cerebellar atrophy, and accumulates abnormally glutamylated tubulin in degenerating neurons. We found biallelic rare and damaging variants in the gene encoding CCP1 in 13 individuals with infantile-onset neurodegeneration and confirmed the absence of functional CCP1 along with dysregulated tubulin polyglutamylation. The human disease mainly affected the cerebellum, spinal motor neurons, and peripheral nerves. We also demonstrate previously unrecognized peripheral nerve and spinal motor neuron degeneration in  mice, which thus recapitulated key features of the human disease. Our findings link human neurodegeneration to tubulin polyglutamylation, entailing this post-translational modification as a potential target for drug development for neurodegenerative disorders.</p>},
	issn = {1460-2075},
	doi = {10.15252/embj.2018100540},
	author = {Shashi, Vandana and Magiera, Maria M and Klein, Dennis and Zaki, Maha and Schoch, Kelly and Rudnik-Sch{\"o}neborn, Sabine and Norman, Andrew and Lopes Abath Neto, Osorio and Dusl, Marina and Yuan, Xidi and Bartesaghi, Luca and De Marco, Patrizia and Alfares, Ahmed A and Marom, Ronit and Arold, Stefan T and Guzm{\'a}n-Vega, Francisco J and Pena, Loren Dm and Smith, Edward C and Steinlin, Maja and Babiker, Mohamed Oe and Mohassel, Payam and Foley, A Reghan and Donkervoort, Sandra and Kaur, Rupleen and Ghosh, Partha S and Stanley, Valentina and Musaev, Damir and Nava, Caroline and Mignot, Cyril and Keren, Boris and Scala, Marcello and Tassano, Elisa and Picco, Paolo and Doneda, Paola and Fiorillo, Chiara and Issa, Mahmoud Y and Alassiri, Ali and Alahmad, Ahmed and Gerard, Amanda and Liu, Pengfei and Yang, Yaping and Ertl-Wagner, Birgit and Kranz, Peter G and Wentzensen, Ingrid M and Stucka, Rolf and Stong, Nicholas and Allen, Andrew S and Goldstein, David B and Schoser, Benedikt and R{\"o}sler, Kai M and Alfadhel, Majid and Capra, Valeria and Chrast, Roman and Strom, Tim M and Kamsteeg, Erik-Jan and B{\"o}nnemann, Carsten G and Gleeson, Joseph G and Martini, Rudolf and Janke, Carsten and Senderek, Jan}
}
@article {334,
	title = {A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay.},
	journal = {Am J Hum Genet},
	volume = {100},
	year = {2017},
	month = {2017 Feb 02},
	pages = {343-351},
	abstract = {<p>Whole-exome sequencing (WES) has increasingly enabled new pathogenic gene variant identification for undiagnosed neurodevelopmental disorders and provided insights into both gene function and disease biology. Here, we describe seven children with a neurodevelopmental disorder characterized by microcephaly, profound developmental delays and/or intellectual disability, cataracts, severe epilepsy including infantile spasms, irritability, failure to thrive, and stereotypic hand movements. Brain imaging in these individuals reveals delay in myelination and cerebral atrophy. We observe an identical recurrent de novo heterozygous c.892C>T (p.Arg298Trp) variant in the nucleus accumbens associated 1 (NACC1) gene in seven affected individuals. One of the seven individuals is mosaic for this variant. NACC1 encodes a transcriptional repressor implicated in gene expression and has not previously been associated with germline disorders. The probability of finding the same missense NACC1 variant by chance in 7 out of 17,228 individuals who~underwent WES for diagnoses of neurodevelopmental phenotypes is extremely small and achieves genome-wide significance (p~= 1.25~{\texttimes} 10). Selective constraint against missense variants in NACC1 makes this excess of an identical missense variant in all seven individuals more remarkable. Our findings are consistent with a germline recurrent mutational hotspot associated with an allele-specific neurodevelopmental phenotype in NACC1.</p>},
	keywords = {Alleles, Amino Acid Sequence, Brain, Cataract, Child, Child, Preschool, Female, Genetic Variation, Genome-Wide Association Study, Humans, Infant, Intellectual Disability, Magnetic Resonance Imaging, Male, Microcephaly, Mutation, Missense, Neoplasm Proteins, Pedigree, Phenotype, Repressor Proteins, Spasms, Infantile},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2016.12.013},
	author = {Schoch, Kelly and Meng, Linyan and Szelinger, Szabolcs and Bearden, David R and Stray-Pedersen, Asbjorg and Busk, Oyvind L and Stong, Nicholas and Liston, Eriskay and Cohn, Ronald D and Scaglia, Fernando and Rosenfeld, Jill A and Tarpinian, Jennifer and Skraban, Cara M and Deardorff, Matthew A and Friedman, Jeremy N and Akdemir, Zeynep Coban and Walley, Nicole and Mikati, Mohamad A and Kranz, Peter G and Jasien, Joan and McConkie-Rosell, Allyn and McDonald, Marie and Wechsler, Stephanie Burns and Freemark, Michael and Kansagra, Sujay and Freedman, Sharon and Bali, Deeksha and Millan, Francisca and Bale, Sherri and Nelson, Stanley F and Lee, Hane and Dorrani, Naghmeh and Goldstein, David B and Xiao, Rui and Yang, Yaping and Posey, Jennifer E and Martinez-Agosto, Julian A and Lupski, James R and Wangler, Michael F and Shashi, Vandana}
}
