TheCHD family of proteins is characterized by the presence ofchromo (chromatin organization modifier) domains andSNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification ofchromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. CHD2 catalyzes the assembly ofchromatin into periodic arrays; and theN-terminal region of CHD2, which contains tandem chromodomains, serves an auto-inhibitory role in both the DNA-binding and ATPase activities of CHD2.[7]Alternatively spliced transcript variants encoding distinctisoforms have been found for this gene.[6]
CHD2 myoclonic encephalopathy is a condition characterized by recurrent seizures (epilepsy), abnormal brain function (encephalopathy), and intellectual disability. Epilepsy begins in childhood, typically between ages 6 months and 4 years. Each individual may experience a variety of seizure types, most commonly myoclonic seizures.[15]
Recently, de novo mutations or deletions in CHD2 has been linked to intellectual disability[16] and to autism.[17][18][19] 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.
Syndromes associated with mutations or deletions in CHD2 can be devastating. Families of individuals with CHD2 mutations or deletions can join the CHD2 Support and Research Group on Facebook[20] or find information and support through the non-profit organization Coalition to Cure CHD2.[21]
^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.
^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.Bibcode:2014Natur.515..216I.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.Bibcode:2014Natur.515..209..doi:10.1038/nature13772.PMC4402723.PMID25363760.
