@article {998, title = {CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity.}, journal = {Epilepsia}, year = {2021}, month = {2021 May 26}, abstract = {

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.

}, issn = {1528-1167}, doi = {10.1111/epi.16931}, author = {Ernst, Michelle E and Baugh, Evan H and Thomas, Amanda and Bier, Louise and Lippa, Natalie and Stong, Nicholas and Mulhern, Maureen S and Kushary, Sulagna and Akman, Cigdem I and Heinzen, Erin L and Yeh, Raymond and Bi, Weimin and Hanchard, Neil A and Burrage, Lindsay C and Leduc, Magalie S and Chong, Josephine S C and Bend, Renee and Lyons, Michael J and Lee, Jennifer A and Suwannarat, Pim and Brilstra, Eva and Simon, Marleen and Koopmans, Marije and van Binsbergen, Ellen and Groepper, Daniel and Fleischer, Julie and Nava, Caroline and Keren, Boris and Mignot, Cyril and Mathieu, Sophie and Mancini, Grazia M S and Madan-Khetarpal, Suneeta and Infante, Elena M and Bluvstein, Judith and Seeley, Andrea and Bachman, Kristine and Klee, Eric W and Schultz-Rogers, Laura E and Hasadsri, Linda and Barnett, Sarah and Ellingson, Marissa S and Ferber, Matthew J and Narayanan, Vinodh and Ramsey, Keri and Rauch, Anita and Joset, Pascal and Steindl, Katharina and Sheehan, Theodore and Poduri, Annapurna and Vasquez, Alejandra and Ruivenkamp, Claudia and White, Susan M and Pais, Lynn and Monaghan, Kristin G and Goldstein, David B and Sands, Tristan T and Aggarwal, Vimla} } @article {670, title = {CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum.}, journal = {Genet Med}, volume = {21}, year = {2019}, month = {2019 12}, pages = {2723-2733}, abstract = {

PURPOSE: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD).

METHODS: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function.

RESULTS: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits.

CONCLUSION: We significantly broaden the mutational and clinical spectrum ofCTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.

}, issn = {1530-0366}, doi = {10.1038/s41436-019-0585-z}, author = {Konrad, Enrico D H and Nardini, Niels and Caliebe, Almuth and Nagel, Inga and Young, Dana and Horvath, Gabriella and Santoro, Stephanie L and Shuss, Christine and Ziegler, Alban and Bonneau, Dominique and Kempers, Marlies and Pfundt, Rolph and Legius, Eric and Bouman, Arjan and Stuurman, Kyra E and {\~O}unap, Katrin and Pajusalu, Sander and Wojcik, Monica H and Vasileiou, Georgia and Le Guyader, Gwena{\"e}l and Schnelle, Hege M and Berland, Siren and Zonneveld-Huijssoon, Evelien and Kersten, Simone and Gupta, Aditi and Blackburn, Patrick R and Ellingson, Marissa S and Ferber, Matthew J and Dhamija, Radhika and Klee, Eric W and McEntagart, Meriel and Lichtenbelt, Klaske D and Kenney, Amy and Vergano, Samantha A and Abou Jamra, Rami and Platzer, Konrad and Ella Pierpont, Mary and Khattar, Divya and Hopkin, Robert J and Martin, Richard J and Jongmans, Marjolijn C J and Chang, Vivian Y and Martinez-Agosto, Julian A and Kuismin, Outi and Kurki, Mitja I and Pietil{\"a}inen, Olli and Palotie, Aarno and Maarup, Timothy J and Johnson, Diana S and Venborg Pedersen, Katja and Laulund, Lone W and Lynch, Sally A and Blyth, Moira and Prescott, Katrina and Canham, Natalie and Ibitoye, Rita and Brilstra, Eva H and Shinawi, Marwan and Fassi, Emily and Sticht, Heinrich and Gregor, Anne and Van Esch, Hilde and Zweier, Christiane} }