@article {790,
	title = {Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.},
	journal = {Brain},
	volume = {143},
	year = {2020},
	month = {2020 05 01},
	pages = {1447-1461},
	abstract = {<p>Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.</p>},
	keywords = {Abnormalities, Multiple, Epileptic Syndromes, Female, Glutamate Decarboxylase, Humans, Infant, Newborn, Male, Mutation, Pedigree},
	issn = {1460-2156},
	doi = {10.1093/brain/awaa085},
	author = {Chatron, Nicolas and Becker, Felicitas and Morsy, Heba and Schmidts, Miriam and Hardies, Katia and Tuysuz, Beyhan and Roselli, Sandra and Najafi, Maryam and Alkaya, Dilek Uludag and Ashrafzadeh, Farah and Nabil, Amira and Omar, Tarek and Maroofian, Reza and Karimiani, Ehsan Ghayoor and Hussien, Haytham and Kok, Fernando and Ramos, Luiza and Gunes, Nilay and Bilguvar, Kaya and Labalme, Audrey and Alix, Eudeline and Sanlaville, Damien and de Bellescize, Julitta and Poulat, Anne-Lise and Moslemi, Ali-Reza and Lerche, Holger and May, Patrick and Lesca, Gaetan and Weckhuysen, Sarah and Tajsharghi, Homa}
}
@article {823,
	title = {Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome.},
	journal = {J Clin Invest},
	volume = {130},
	year = {2020},
	month = {2020 08 03},
	pages = {4423-4439},
	abstract = {<p>Joubert syndrome (JBTS) is a recessive neurodevelopmental ciliopathy characterized by a pathognomonic hindbrain malformation. All known JBTS genes encode proteins involved in the structure or function of primary cilia, ubiquitous antenna-like organelles essential for cellular signal transduction. Here, we used the recently identified JBTS-associated protein armadillo repeat motif-containing 9 (ARMC9) in tandem-affinity purification and yeast 2-hybrid screens to identify a ciliary module whose dysfunction underlies JBTS. In addition to the known JBTS-associated proteins CEP104 and CSPP1, we identified coiled-coil domain containing 66 (CCDC66) and TOG array regulator of axonemal microtubules 1 (TOGARAM1) as ARMC9 interaction partners. We found that TOGARAM1 variants cause JBTS and disrupt TOGARAM1 interaction with ARMC9. Using a combination of protein interaction analyses, characterization of patient-derived fibroblasts, and analysis of CRISPR/Cas9-engineered zebrafish and hTERT-RPE1 cells, we demonstrated that dysfunction of ARMC9 or TOGARAM1 resulted in short cilia with decreased axonemal acetylation and polyglutamylation, but relatively intact transition zone function. Aberrant serum-induced ciliary resorption and cold-induced depolymerization in ARMC9 and TOGARAM1 patient cell lines suggest a role for this new JBTS-associated protein module in ciliary stability.</p>},
	keywords = {Abnormalities, Multiple, Acetylation, Animals, Armadillo Domain Proteins, Cerebellum, Cilia, CRISPR-Cas Systems, Disease Models, Animal, Eye Abnormalities, Humans, Kidney Diseases, Cystic, Peptides, Retina, Zebrafish, Zebrafish Proteins},
	issn = {1558-8238},
	doi = {10.1172/JCI131656},
	author = {Latour, Brooke L and Van De Weghe, Julie C and Rusterholz, Tamara Ds and Letteboer, Stef Jf and Gomez, Arianna and Shaheen, Ranad and Gesemann, Matthias and Karamzade, Arezou and Asadollahi, Mostafa and Barroso-Gil, Miguel and Chitre, Manali and Grout, Megan E and van Reeuwijk, Jeroen and van Beersum, Sylvia Ec and Miller, Caitlin V and Dempsey, Jennifer C and Morsy, Heba and Bamshad, Michael J and Nickerson, Deborah A and Neuhauss, Stephan Cf and Boldt, Karsten and Ueffing, Marius and Keramatipour, Mohammad and Sayer, John A and Alkuraya, Fowzan S and Bachmann-Gagescu, Ruxandra and Roepman, Ronald and Doherty, Dan}
}
