KEGG   DISEASE: Autosomal dominant mental retardationHelp
Entry
H00773                      Disease                                

Name
Autosomal dominant mental retardation
Description
Mental retardation (MR) is a neurodevelopmental disorder characterized by low intelligence quotient (IQ) and deficits in adaptive behaviors. Most MR genes identified so far were either located on the X chromosome or are associated with an autosomal recessive mode of inheritance. Recently, a lot of genes associated with autosomal dominant mental retardation have been identified.
Category
Mental and behavioural disorder
Brite
Human diseases [BR:br08402]
 Other diseases
  Mental and behavioural disorders
   H00773  Autosomal dominant mental retardation
Human diseases in ICD-11 classification [BR:br08403]
 06 Mental, behavioural or neurodevelopmental disorders
  Neurodevelopmental disorders
   6A00  Disorders of intellectual development
    H00773  Autosomal dominant mental retardation
BRITE hierarchy
Pathway
hsa04728 Dopaminergic synapse   
hsa04261 Adrenergic signaling in cardiomyocytes   
hsa04024 cAMP signaling pathway   
Gene
(MRD1) MBD5 [HSA:55777]
(MRD2) DOCK8 [HSA:81704] [KO:K21852]
(MRD3) CDH15 [HSA:1013] [KO:K06809]
(MRD4) KIRREL3 [HSA:84623]
(MRD5) SYNGAP1 [HSA:8831] [KO:K17631]
(MRD6) GRIN2B [HSA:2904] [KO:K05210]
(MRD7) DYRK1A [HSA:1859] [KO:K08825]
(MRD8) GRIN1 [HSA:2902] [KO:K05208]
(MRD9) KIF1A [HSA:547] [KO:K10392]
(MRD10) CACNG2 [HSA:10369] [KO:K04867]
(MRD11) EPB41L1 [HSA:2036] [KO:K06107]
(MRD12) ARID1B [HSA:57492] [KO:K11653]
(MRD13) DYNC1H1 [HSA:1778] [KO:K10413]
(MRD14) ARID1A [HSA:8289] [KO:K11653]
(MRD15) SMARCB1 [HSA:6598] [KO:K11648]
(MRD16) SMARCA4 [HSA:6597] [KO:K11647]
(MRD17) PACS1 [HSA:55690]
(MRD18) GATAD2B [HSA:57459]
(MRD19) CTNNB1 [HSA:1499] [KO:K02105]
(MRD20) MEF2C [HSA:4208] [KO:K04454]
(MRD21) CTCF [HSA:10664]
(MRD22) ZBTB18 [HSA:10472]
(MRD23) SETD5 [HSA:55209]
(MRD24) DEAF1 [HSA:10522]
(MRD25) AHDC1 [HSA:27245] [KO:K22592]
(MRD26) AUTS2 [HSA:26053]
(MRD27) SOX11 [HSA:6664] [KO:K09268]
(MRD29) SETBP1 [HSA:26040]
(MRD30) ZMYND11 [HSA:10771]
(MRD31) PURA [HSA:5813] [KO:K21772]
(MRD32) KAT6A [HSA:7994] [KO:K11305]
(MRD33) DPP6 [HSA:1804]
(MRD34) COL4A3BP [HSA:10087] [KO:K08283]
(MRD35) PPP2R5D [HSA:5528] [KO:K11584]
(MRD36) PPP2R1A [HSA:5518] [KO:K03456]
(MRD38) EEF1A2 [HSA:1917] [KO:K03231]
(MRD39) MYT1L [HSA:23040]
(MRD40) CHAMP1 [HSA:283489] [KO:K22593]
(MRD42) GNB1 [HSA:2782] [KO:K04536]
(MRD43) HIVEP2 [HSA:3097] [KO:K09239]
(MRD44) TRIO [HSA:7204] [KO:K08810]
(MRD45) CIC [HSA:23152] [KO:K20225]
(MRD46) KCNQ5 [HSA:56479] [KO:K04930]
(MRD47) STAG1 [HSA:10274] [KO:K06671]
(MRD48) RAC1 [HSA:5879] [KO:K04392]
(MRD49) TRIP12 [HSA:9320] [KO:K10590]
(MRD50) NAA15 [HSA:80155] [KO:K20792]
(MRD51) KMT5B [HSA:51111] [KO:K11429]
(MRD52) ASH1L [HSA:55870] [KO:K06101]
(MRD53) CAMK2A [HSA:815] [KO:K04515]
(MRD54) CAMK2B [HSA:816] [KO:K04515]
(MRD61) RUSC2 [HSA:9853]
Other DBs
ICD-11: 6A00
ICD-10: F78.9
MeSH: C566947 C567241 C567240 C567234
OMIM: 156200 614113 612580 612581 612621 613970 614254 614255 614256 614257 614562 614563 614607 614608 614609 615009 615074 615075 613443 615502 612337 615761 615828 615829 615866 616078 616083 616158 616268 616311 616351 616355 616362 616393 616521 616579 616973 616977 617061 617600 617601 617635 617751 617752 617787 617788 617796 617798 617799
Reference
  Authors
Williams SR, Mullegama SV, Rosenfeld JA, Dagli AI, Hatchwell E, Allen WP, Williams CA, Elsea SH
  Title
Haploinsufficiency of MBD5 associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures.
  Journal
Eur J Hum Genet 18:436-41 (2010)
DOI:10.1038/ejhg.2009.199
Reference
  Authors
Griggs BL, Ladd S, Saul RA, DuPont BR, Srivastava AK
  Title
Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities.
  Journal
Genomics 91:195-202 (2008)
DOI:10.1016/j.ygeno.2007.10.011
Reference
  Authors
Bhalla K, Luo Y, Buchan T, Beachem MA, Guzauskas GF, Ladd S, Bratcher SJ, Schroer RJ, Balsamo J, DuPont BR, Lilien J, Srivastava AK
  Title
Alterations in CDH15 and KIRREL3 in patients with mild to severe intellectual disability.
  Journal
Am J Hum Genet 83:703-13 (2008)
DOI:10.1016/j.ajhg.2008.10.020
Reference
  Authors
Huang K
  Title
SYNGAP: bridging the gap between genetic factors and autosomal non-syndromic mental retardation.
  Journal
Clin Genet 76:149-51 (2009)
DOI:10.1111/j.1399-0004.2009.01247_3.x
Reference
  Authors
Endele S, Rosenberger G, Geider K, Popp B, Tamer C, Stefanova I, Milh M, Kortum F, Fritsch A, Pientka FK, Hellenbroich Y, Kalscheuer VM, Kohlhase J, Moog U, Rappold G, Rauch A, Ropers HH, von Spiczak S, Tonnies H, Villeneuve N, Villard L, Zabel B, Zenker M, Laube B, Reis A, Wieczorek D, Van Maldergem L, Kutsche K
  Title
Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes.
  Journal
Nat Genet 42:1021-6 (2010)
DOI:10.1038/ng.677
Reference
  Authors
van Bon BW, Hoischen A, Hehir-Kwa J, de Brouwer AP, Ruivenkamp C, Gijsbers AC, Marcelis CL, de Leeuw N, Veltman JA, Brunner HG, de Vries BB
  Title
Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly.
  Journal
Clin Genet 79:296-9 (2011)
DOI:10.1111/j.1399-0004.2010.01544.x
Reference
PMID:21376300 (MRD8, MRD9, MRD10, MRD11)
  Authors
Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O, Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, D'Anjou G, Vanasse M, Srour M, Lafreniere RG, Drapeau P, Lacaille JC, Kim E, Lee JR, Igarashi K, Huganir RL, Rouleau GA, Michaud JL
  Title
Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.
  Journal
Am J Hum Genet 88:306-16 (2011)
DOI:10.1016/j.ajhg.2011.02.001
Reference
  Authors
Willemsen MH, Vissers LE, Willemsen MA, van Bon BW, Kroes T, de Ligt J, de Vries BB, Schoots J, Lugtenberg D, Hamel BC, van Bokhoven H, Brunner HG, Veltman JA, Kleefstra T
  Title
Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects.
  Journal
J Med Genet 49:179-83 (2012)
DOI:10.1136/jmedgenet-2011-100542
Reference
PMID:22426308 (MRD12, MRD14, MRD15, MRD16)
  Authors
Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N
  Title
Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome.
  Journal
Nat Genet 44:376-8 (2012)
DOI:10.1038/ng.2219
Reference
  Authors
Schuurs-Hoeijmakers JH, Oh EC, Vissers LE, Swinkels ME, Gilissen C, Willemsen MA, Holvoet M, Steehouwer M, Veltman JA, de Vries BB, van Bokhoven H, de Brouwer AP, Katsanis N, Devriendt K, Brunner HG
  Title
Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome.
  Journal
Am J Hum Genet 91:1122-7 (2012)
DOI:10.1016/j.ajhg.2012.10.013
Reference
  Authors
Willemsen MH, Nijhof B, Fenckova M, Nillesen WM, Bongers EM, Castells-Nobau A, Asztalos L, Viragh E, van Bon BW, Tezel E, Veltman JA, Brunner HG, de Vries BB, de Ligt J, Yntema HG, van Bokhoven H, Isidor B, Le Caignec C, Lorino E, Asztalos Z, Koolen DA, Vissers LE, Schenck A, Kleefstra T
  Title
GATAD2B loss-of-function mutations cause a recognisable syndrome with intellectual disability and are associated with learning deficits and synaptic undergrowth in Drosophila.
  Journal
J Med Genet 50:507-14 (2013)
DOI:10.1136/jmedgenet-2012-101490
Reference
PMID:23033978 (MRD19)
  Authors
de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, Vulto-van Silfhout AT, Koolen DA, de Vries P, Gilissen C, del Rosario M, Hoischen A, Scheffer H, de Vries BB, Brunner HG, Veltman JA, Vissers LE
  Title
Diagnostic exome sequencing in persons with severe intellectual disability.
  Journal
N Engl J Med 367:1921-9 (2012)
DOI:10.1056/NEJMoa1206524
Reference
  Authors
Zweier M, Gregor A, Zweier C, Engels H, Sticht H, Wohlleber E, Bijlsma EK, Holder SE, Zenker M, Rossier E, Grasshoff U, Johnson DS, Robertson L, Firth HV, Ekici AB, Reis A, Rauch A
  Title
Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression.
  Journal
Hum Mutat 31:722-33 (2010)
DOI:10.1002/humu.21253
Reference
  Authors
Gregor A, Oti M, Kouwenhoven EN, Hoyer J, Sticht H, Ekici AB, Kjaergaard S, Rauch A, Stunnenberg HG, Uebe S, Vasileiou G, Reis A, Zhou H, Zweier C
  Title
De novo mutations in the genome organizer CTCF cause intellectual disability.
  Journal
Am J Hum Genet 93:124-31 (2013)
DOI:10.1016/j.ajhg.2013.05.007
Reference
PMID:21800092 (MRD22)
  Authors
Ballif BC, Rosenfeld JA, Traylor R, Theisen A, Bader PI, Ladda RL, Sell SL, Steinraths M, Surti U, McGuire M, Williams S, Farrell SA, Filiano J, Schnur RE, Coffey LB, Tervo RC, Stroud T, Marble M, Netzloff M, Hanson K, Aylsworth AS, Bamforth JS, Babu D, Niyazov DM, Ravnan JB, Schultz RA, Lamb AN, Torchia BS, Bejjani BA, Shaffer LG
  Title
High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44.
  Journal
Hum Genet 131:145-56 (2012)
DOI:10.1007/s00439-011-1073-y
Reference
  Authors
Grozeva D, Carss K, Spasic-Boskovic O, Parker MJ, Archer H, Firth HV, Park SM, Canham N, Holder SE, Wilson M, Hackett A, Field M, Floyd JA, Hurles M, Raymond FL
  Title
De novo loss-of-function mutations in SETD5, encoding a methyltransferase in a 3p25 microdeletion syndrome critical region, cause intellectual disability.
  Journal
Am J Hum Genet 94:618-24 (2014)
DOI:10.1016/j.ajhg.2014.03.006
Reference
  Authors
Xia F, Bainbridge MN, Tan TY, Wangler MF, Scheuerle AE, Zackai EH, Harr MH, Sutton VR, Nalam RL, Zhu W, Nash M, Ryan MM, Yaplito-Lee J, Hunter JV, Deardorff MA, Penney SJ, Beaudet AL, Plon SE, Boerwinkle EA, Lupski JR, Eng CM, Muzny DM, Yang Y, Gibbs RA
  Title
De novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea.
  Journal
Am J Hum Genet 94:784-9 (2014)
DOI:10.1016/j.ajhg.2014.04.006
Reference
  Title
Large-scale discovery of novel genetic causes of developmental disorders.
  Journal
Nature 519:223-8 (2015)
DOI:10.1038/nature14135
Reference
  Authors
Tham E, Lindstrand A, Santani A, Malmgren H, Nesbitt A, Dubbs HA, Zackai EH, Parker MJ, Millan F, Rosenbaum K, Wilson GN, Nordgren A
  Title
Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features.
  Journal
Am J Hum Genet 96:507-13 (2015)
DOI:10.1016/j.ajhg.2015.01.016
Reference
  Authors
Liao C, Fu F, Li R, Yang WQ, Liao HY, Yan JR, Li J, Li SY, Yang X, Li DZ
  Title
Loss-of-function variation in the DPP6 gene is associated with autosomal dominant microcephaly and mental retardation.
  Journal
Eur J Med Genet 56:484-9 (2013)
DOI:10.1016/j.ejmg.2013.06.008
Reference
  Authors
Nakajima J, Okamoto N, Tohyama J, Kato M, Arai H, Funahashi O, Tsurusaki Y, Nakashima M, Kawashima H, Saitsu H, Matsumoto N, Miyake N
  Title
De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy.
  Journal
Clin Genet 87:356-61 (2015)
DOI:10.1111/cge.12394
Reference
  Authors
De Rocker N, Vergult S, Koolen D, Jacobs E, Hoischen A, Zeesman S, Bang B, Bena F, Bockaert N, Bongers EM, de Ravel T, Devriendt K, Giglio S, Faivre L, Joss S, Maas S, Marle N, Novara F, Nowaczyk MJ, Peeters H, Polstra A, Roelens F, Rosenberg C, Thevenon J, Tumer Z, Vanhauwaert S, Varvagiannis K, Willaert A, Willemsen M, Willems M, Zuffardi O, Coucke P, Speleman F, Eichler EE, Kleefstra T, Menten B
  Title
Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity.
  Journal
Genet Med 17:460-6 (2015)
DOI:10.1038/gim.2014.124
Reference
  Authors
Petrovski S, Kury S, Myers CT, Anyane-Yeboa K, Cogne B, Bialer M, Xia F, Hemati P, Riviello J, Mehaffey M, Besnard T, Becraft E, Wadley A, Politi AR, Colombo S, Zhu X, Ren Z, Andrews I, Dudding-Byth T, Schneider AL, Wallace G, Rosen AB, Schelley S, Enns GM, Corre P, Dalton J, Mercier S, Latypova X, Schmitt S, Guzman E, Moore C, Bier L, Heinzen EL, Karachunski P, Shur N, Grebe T, Basinger A, Nguyen JM, Bezieau S, Wierenga K, Bernstein JA, Scheffer IE, Rosenfeld JA, Mefford HC, Isidor B, Goldstein DB
  Title
Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures.
  Journal
Am J Hum Genet 98:1001-10 (2016)
DOI:10.1016/j.ajhg.2016.03.011
Reference
  Authors
Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Ropke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, Wohlleber E, Zweier C, Ekici AB, Zink AM, Rump A, Meisinger C, Grallert H, Sticht H, Schenck A, Engels H, Rappold G, Schrock E, Wieacker P, Riess O, Meitinger T, Reis A, Strom TM
  Title
Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.
  Journal
Lancet 380:1674-82 (2012)
DOI:10.1016/S0140-6736(12)61480-9
Reference
  Authors
Stessman HA, Xiong B, Coe BP, Wang T, Hoekzema K, Fenckova M, Kvarnung M, Gerdts J, Trinh S, Cosemans N, Vives L, Lin J, Turner TN, Santen G, Ruivenkamp C, Kriek M, van Haeringen A, Aten E, Friend K, Liebelt J, Barnett C, Haan E, Shaw M, Gecz J, Anderlid BM, Nordgren A, Lindstrand A, Schwartz C, Kooy RF, Vandeweyer G, Helsmoortel C, Romano C, Alberti A, Vinci M, Avola E, Giusto S, Courchesne E, Pramparo T, Pierce K, Nalabolu S, Amaral DG, Scheffer IE, Delatycki MB, Lockhart PJ, Hormozdiari F, Harich B, Castells-Nobau A, Xia K, Peeters H, Nordenskjold M, Schenck A, Bernier RA, Eichler EE
  Title
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
  Journal
Nat Genet 49:515-526 (2017)
DOI:10.1038/ng.3792
Reference
  Authors
Kury S, van Woerden GM, Besnard T, Proietti Onori M, Latypova X, Towne MC, Cho MT, Prescott TE, Ploeg MA, Sanders S, Stessman HAF, Pujol A, Distel B, Robak LA, Bernstein JA, Denomme-Pichon AS, Lesca G, Sellars EA, Berg J, Carre W, Busk OL, van Bon BWM, Waugh JL, Deardorff M, Hoganson GE, Bosanko KB, Johnson DS, Dabir T, Holla OL, Sarkar A, Tveten K, de Bellescize J, Braathen GJ, Terhal PA, Grange DK, van Haeringen A, Lam C, Mirzaa G, Burton J, Bhoj EJ, Douglas J, Santani AB, Nesbitt AI, Helbig KL, Andrews MV, Begtrup A, Tang S, van Gassen KLI, Juusola J, Foss K, Enns GM, Moog U, Hinderhofer K, Paramasivam N, Lincoln S, Kusako BH, Lindenbaum P, Charpentier E, Nowak CB, Cherot E, Simonet T, Ruivenkamp CAL, Hahn S, Brownstein CA, Xia F, Schmitt S, Deb W, Bonneau D, Nizon M, Quinquis D, Chelly J, Rudolf G, Sanlaville D, Parent P, Gilbert-Dussardier B, Toutain A, Sutton VR, Thies J, Peart-Vissers LELM, Boisseau P, Vincent M, Grabrucker AM, Dubourg C, Tan WH, Verbeek NE, Granzow M, Santen GWE, Shendure J, Isidor B, Pasquier L, Redon R, Yang Y, State MW, Kleefstra T, Cogne B, Petrovski S, Retterer K, Eichler EE, Rosenfeld JA, Agrawal PB, Bezieau S, Odent S, Elgersma Y, Mercier S
  Title
De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability.
  Journal
Am J Hum Genet 101:768-788 (2017)
DOI:10.1016/j.ajhg.2017.10.003

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