The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. CHD2 catalyzes the assembly of chromatin into periodic arrays; and the N-terminal region of CHD2, which contains tandem chromodomains, serves an auto-inhibitory role in both the DNA-binding and ATPase activities of CHD2.[3]Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[2]
Clinical significance
De Novo Mutations and deletions in this gene have been associated with cases of epileptic encephalopathies.[4][5][6][7][8]
Recently, de novo mutations or deletions in CHD2 has been linked to intellectual disability[11] and to autism.[12][13][14] Researchers found 27 genes which abolish function of the corresponding protein — in at least two people with autism, and 6 genes are mutated in three or more people with autism. These six genes — CHD8, DYRK1A, ANK2, GRIN2B, DSCAM and CHD2 — are the strongest autism candidates identified so far.
Family support
Syndromes associated with mutations or deletions in CHD2 can be devastating. Families of individuals with CHD2 mutations or deletions can join a research and support group.[15]
↑Courage C, Houge G, Gallati S, Schjelderup J, Rieubland C (Sep 2014). "15q26.1 microdeletion encompassing only CHD2 and RGMA in two adults with moderate intellectual disability, epilepsy and truncal obesity". European Journal of Medical Genetics. 57 (9): 520–3. doi:10.1016/j.ejmg.2014.06.003. PMID24932903.
↑Lund C, Brodtkorb E, Øye AM, Røsby O, Selmer KK (Apr 2014). "CHD2 mutations in Lennox-Gastaut syndrome". Epilepsy & Behavior. 33: 18–21. doi:10.1016/j.yebeh.2014.02.005. PMID24614520.
↑Capelli LP, Krepischi AC, Gurgel-Giannetti J, Mendes MF, Rodrigues T, Varela MC, Koiffmann CP, Rosenberg C (Feb 2012). "Deletion of the RMGA and CHD2 genes in a child with epilepsy and mental deficiency". European Journal of Medical Genetics. 55 (2): 132–4. doi:10.1016/j.ejmg.2011.10.004. PMID22178256.
↑Iossifov I, O'Roak BJ, Sanders SJ, Ronemus M, Krumm N, Levy D, Stessman HA, Witherspoon KT, Vives L, Patterson KE, Smith JD, Paeper B, Nickerson DA, Dea J, Dong S, Gonzalez LE, Mandell JD, Mane SM, Murtha MT, Sullivan CA, Walker MF, Waqar Z, Wei L, Willsey AJ, Yamrom B, Lee YH, Grabowska E, Dalkic E, Wang Z, Marks S, Andrews P, Leotta A, Kendall J, Hakker I, Rosenbaum J, Ma B, Rodgers L, Troge J, Narzisi G, Yoon S, Schatz MC, Ye K, McCombie WR, Shendure J, Eichler EE, State MW, Wigler M (Nov 2014). "The contribution of de novo coding mutations to autism spectrum disorder". Nature. 515 (7526): 216–21. doi:10.1038/nature13908. PMC4313871. PMID25363768.
↑De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton PF, Brownfeld JM, Cai J, Campbell NG, Carracedo A, Chahrour MH, Chiocchetti AG, Coon H, Crawford EL, Curran SR, Dawson G, Duketis E, Fernandez BA, Gallagher L, Geller E, Guter SJ, Hill RS, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck SM, Kolevzon A, Lee I, Lei I, Lei J, Lehtimäki T, Lin CF, Ma'ayan A, Marshall CR, McInnes AL, Neale B, Owen MJ, Ozaki N, Parellada M, Parr JR, Purcell S, Puura K, Rajagopalan D, Rehnström K, Reichenberg A, Sabo A, Sachse M, Sanders SJ, Schafer C, Schulte-Rüther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss LA, Willsey AJ, Yu TW, Yuen RK, Cook EH, Freitag CM, Gill M, Hultman CM, Lehner T, Palotie A, Schellenberg GD, Sklar P, State MW, Sutcliffe JS, Walsh CA, Scherer SW, Zwick ME, Barett JC, Cutler DJ, Roeder K, Devlin B, Daly MJ, Buxbaum JD (Nov 2014). "Synaptic, transcriptional and chromatin genes disrupted in autism". Nature. 515 (7526): 209–15. doi:10.1038/nature13772. PMC4402723. PMID25363760.
Feys T, Poppe B, De Preter K, Van Roy N, Verhasselt B, De Paepe P, De Paepe A, Speleman F (Jul 2007). "A detailed inventory of DNA copy number alterations in four commonly used Hodgkin's lymphoma cell lines". Haematologica. 92 (7): 913–20. doi:10.3324/haematol.11073. PMID17606441.