| H00658 | |
| H number | H00658 |
| Name | X-linked syndromic intellectual developmental disorder; Syndromic X-linked mental retardation |
| Description | X-linked intellectual developmental disorder (XLID), formerly known as X-linked mental retardation, is an inherited condition that causes failure to develop cognitive abilities because of mutations in several genes on the X chromosome. XLID is subdivided into syndromic and non-syndromic forms, depending on whether further abnormalities are found or not. X-linked syndromic intellectual developmental disorder is characterized by recognizable dysmorphic features, neurological complications, and/or metabolic abnormalities. |
| Category | Mental and behavioural disorder |
| Network | nt06509(H00658) DNA replication |
| Gene | (MRXST) HUWE1 [HSA:10075] [KO:K10592] (MRXSSD) PHF8 [HSA:23133] [KO:K19415] (MRXSC) CUL4B [HSA:8450] [KO:K10609] (MRXSR) ZDHHC9 [HSA:51114] [KO:K25778] (MRXSH) ATP6AP2 [HSA:10159] [KO:K19514] (MRXSCJ) KDM5C [HSA:8242] [KO:K11446] (MRXSW) GRIA3 [HSA:2892] [KO:K05199] (MRXSB) HNRNPH2 [HSA:3188] [KO:K12898] (MRXSHG) CNKSR2 [HSA:22866] [KO:K17536] (MRXSN) UBE2A [HSA:7319] [KO:K10573] (MRXSBA) MSL3 [HSA:10943] [KO:K18403] (MRXSA) FAM50A [HSA:9130] [KO:K13119] (MRXSHD) NKAP [HSA:79576] [KO:K25931] (MRXSPM) HS6ST2 [HSA:90161] [KO:K08102] (VEODS) POLA1 [HSA:5422] [KO:K02320] (MRGH) SOX3 [HSA:6658] [KO:K09267] (MRX60) OPHN1 [HSA:4983] [KO:K20650] (MRXSRC) CLCN4 [HSA:1183] [KO:K05012] (MRXSSB) DDX3X [HSA:1654] [KO:K11594] (TOKAS) RLIM [HSA:51132] [KO:K16271] (PGS) AP1S2 [HSA:8905] [KO:K12394] (MRXS11) RBMX [HSA:27316] [KO:K12885] (MRXS13) MECP2 [HSA:4204] [KO:K11588] (MRXS14) UPF3B [HSA:65109] [KO:K14328] (MRXS32) CLIC2 [HSA:1193] [KO:K05022] (MRXS33) TAF1 [HSA:6872] [KO:K03125] (MRXS34) NONO [HSA:4841] [KO:K13214] (MRXS35) RPL10 [HSA:6134] [KO:K02866] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 6A00 ICD-10: F78.9 MeSH: D038901 OMIM: 309590 300263 300354 300799 300423 300534 300699 300986 301008 300860 301032 300261 301039 301025 301030 300123 300486 300114 300958 300978 304340 300238 300055 300260 300676 300886 300966 300967 300998 |
| Reference | PMID:18252223 (HUWE1) AUTHORS Froyen G, Corbett M, Vandewalle J, Jarvela I, Lawrence O, Meldrum C, Bauters M, Govaerts K, Vandeleur L, Van Esch H, Chelly J, Sanlaville D, van Bokhoven H, Ropers HH, Laumonnier F, Ranieri E, Schwartz CE, Abidi F, Tarpey PS, Futreal PA, Whibley A, Raymond FL, Stratton MR, Fryns JP, Scott R, Peippo M, Sipponen M, Partington M, Mowat D, Field M, Hackett A, Marynen P, Turner G, Gecz J TITLE Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. JOURNAL Am J Hum Genet 82:432-43 (2008) DOI:10.1016/j.ajhg.2007.11.002 PMID:20548336 (PHF8) AUTHORS Qiu J, Shi G, Jia Y, Li J, Wu M, Li J, Dong S, Wong J TITLE The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation. JOURNAL Cell Res 20:908-18 (2010) DOI:10.1038/cr.2010.81 PMID:21816345 (CUL4B) AUTHORS Nakagawa T, Xiong Y TITLE X-linked mental retardation gene CUL4B targets ubiquitylation of H3K4 methyltransferase component WDR5 and regulates neuronal gene expression. JOURNAL Mol Cell 43:381-91 (2011) DOI:10.1016/j.molcel.2011.05.033 PMID:17436253 (ZDHHC9) AUTHORS Raymond FL, Tarpey PS, Edkins S, Tofts C, O'Meara S, Teague J, Butler A, Stevens C, Barthorpe S, Buck G, Cole J, Dicks E, Gray K, Halliday K, Hills K, Hinton J, Jones D, Menzies A, Perry J, Raine K, Shepherd R, Small A, Varian J, Widaa S, Mallya U, Moon J, Luo Y, Shaw M, Boyle J, Kerr B, Turner G, Quarrell O, Cole T, Easton DF, Wooster R, Bobrow M, Schwartz CE, Gecz J, Stratton MR, Futreal PA TITLE Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause X-linked mental retardation associated with a Marfanoid habitus. JOURNAL Am J Hum Genet 80:982-7 (2007) DOI:10.1086/513609 PMID:15746149 (ATP6AP2) AUTHORS Ramser J, Abidi FE, Burckle CA, Lenski C, Toriello H, Wen G, Lubs HA, Engert S, Stevenson RE, Meindl A, Schwartz CE, Nguyen G TITLE A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor. JOURNAL Hum Mol Genet 14:1019-27 (2005) DOI:10.1093/hmg/ddi094 PMID:21575681 (KDM5C) AUTHORS Santos-Reboucas CB, Fintelman-Rodrigues N, Jensen LR, Kuss AW, Ribeiro MG, Campos M Jr, Santos JM, Pimentel MM TITLE A novel nonsense mutation in KDM5C/JARID1C gene causing intellectual disability, short stature and speech delay. JOURNAL Neurosci Lett 498:67-71 (2011) DOI:10.1016/j.neulet.2011.04.065 PMID:19449417 (GRIA3) AUTHORS Bonnet C, Leheup B, Beri M, Philippe C, Gregoire MJ, Jonveaux P TITLE Aberrant GRIA3 transcripts with multi-exon duplications in a family with X-linked mental retardation. JOURNAL Am J Med Genet A 149A:1280-9 (2009) DOI:10.1002/ajmg.a.32858 PMID:27545675 (HNRNPH2) AUTHORS Bain JM, Cho MT, Telegrafi A, Wilson A, Brooks S, Botti C, Gowans G, Autullo LA, Krishnamurthy V, Willing MC, Toler TL, Ben-Zev B, Elpeleg O, Shen Y, Retterer K, Monaghan KG, Chung WK TITLE Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females. JOURNAL Am J Hum Genet 99:728-734 (2016) DOI:10.1016/j.ajhg.2016.06.028 PMID:28098945 (CNKSR2) AUTHORS Damiano JA, Burgess R, Kivity S, Lerman-Sagie T, Afawi Z, Scheffer IE, Berkovic SF, Hildebrand MS TITLE Frequency of CNKSR2 mutation in the X-linked epilepsy-aphasia spectrum. JOURNAL Epilepsia 58:e40-e43 (2017) DOI:10.1111/epi.13666 PMID:16909393 (UBE2A) AUTHORS Nascimento RM, Otto PA, de Brouwer AP, Vianna-Morgante AM TITLE UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome. JOURNAL Am J Hum Genet 79:549-55 (2006) DOI:10.1086/507047 PMID:30224647 (MSL3) AUTHORS Basilicata MF, Bruel AL, Semplicio G, Valsecchi CIK, Aktas T, Duffourd Y, Rumpf T, Morton J, Bache I, Szymanski WG, Gilissen C, Vanakker O, Ounap K, Mittler G, van der Burgt I, El Chehadeh S, Cho MT, Pfundt R, Tan TY, Kirchhoff M, Menten B, Vergult S, Lindstrom K, Reis A, Johnson DS, Fryer A, McKay V, Fisher RB, Thauvin-Robinet C, Francis D, Roscioli T, Pajusalu S, Radtke K, Ganesh J, Brunner HG, Wilson M, Faivre L, Kalscheuer VM, Thevenon J, Akhtar A TITLE De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation. JOURNAL Nat Genet 50:1442-1451 (2018) DOI:10.1038/s41588-018-0220-y PMID:32703943 (FAM50A) AUTHORS Lee YR, Khan K, Armfield-Uhas K, Srikanth S, Thompson NA, Pardo M, Yu L, Norris JW, Peng Y, Gripp KW, Aleck KA, Li C, Spence E, Choi TI, Kwon SJ, Park HM, Yu D, Do Heo W, Mooney MR, Baig SM, Wentzensen IM, Telegrafi A, McWalter K, Moreland T, Roadhouse C, Ramsey K, Lyons MJ, Skinner C, Alexov E, Katsanis N, Stevenson RE, Choudhary JS, Adams DJ, Kim CH, Davis EE, Schwartz CE TITLE Mutations in FAM50A suggest that Armfield XLID syndrome is a spliceosomopathy. JOURNAL Nat Commun 11:3698 (2020) DOI:10.1038/s41467-020-17452-6 PMID:31587868 (NKAP) AUTHORS Fiordaliso SK, Iwata-Otsubo A, Ritter AL, Quesnel-Vallieres M, Fujiki K, Nishi E, Hancarova M, Miyake N, Morton JEV, Lee S, Hackmann K, Bando M, Masuda K, Nakato R, Arakawa M, Bhoj E, Li D, Hakonarson H, Takeda R, Harr M, Keena B, Zackai EH, Okamoto N, Mizuno S, Ko JM, Valachova A, Prchalova D, Vlckova M, Pippucci T, Seiler C, Choi M, Matsumoto N, Di Donato N, Barash Y, Sedlacek Z, Shirahige K, Izumi K TITLE Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment. JOURNAL Am J Hum Genet 105:987-995 (2019) DOI:10.1016/j.ajhg.2019.09.009 PMID:30471091 (HS6ST2) AUTHORS Paganini L, Hadi LA, Chetta M, Rovina D, Fontana L, Colapietro P, Bonaparte E, Pezzani L, Marchisio P, Tabano SM, Costanza J, Sirchia SM, Riboni L, Milani D, Miozzo M TITLE A HS6ST2 gene variant associated with X-linked intellectual disability and severe myopia in two male twins. JOURNAL Clin Genet 95:368-374 (2019) DOI:10.1111/cge.13485 PMID:31006512 (POLA1) AUTHORS Van Esch H, Colnaghi R, Freson K, Starokadomskyy P, Zankl A, Backx L, Abramowicz I, Outwin E, Rohena L, Faulkner C, Leong GM, Newbury-Ecob RA, Challis RC, Ounap K, Jaeken J, Seuntjens E, Devriendt K, Burstein E, Low KJ, O'Driscoll M TITLE Defective DNA Polymerase alpha-Primase Leads to X-Linked Intellectual Disability Associated with Severe Growth Retardation, Microcephaly, and Hypogonadism. JOURNAL Am J Hum Genet 104:957-967 (2019) DOI:10.1016/j.ajhg.2019.03.006 PMID:12428212 (SOX3) AUTHORS Laumonnier F, Ronce N, Hamel BC, Thomas P, Lespinasse J, Raynaud M, Paringaux C, Van Bokhoven H, Kalscheuer V, Fryns JP, Chelly J, Moraine C, Briault S TITLE Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency. JOURNAL Am J Hum Genet 71:1450-5 (2002) DOI:10.1086/344661 PMID:20528889 (OPHN1) AUTHORS Al-Owain M, Kaya N, Al-Zaidan H, Al-Hashmi N, Al-Bakheet A, Al-Muhaizea M, Chedrawi A, Basran RK, Milunsky A TITLE Novel intragenic deletion in OPHN1 in a family causing XLMR with cerebellar hypoplasia and distinctive facial appearance. JOURNAL Clin Genet 79:363-70 (2011) DOI:10.1111/j.1399-0004.2010.01462.x PMID:27550844 (CLCN4) AUTHORS Palmer EE, Stuhlmann T, Weinert S, Haan E, Van Esch H, Holvoet M, Boyle J, Leffler M, Raynaud M, Moraine C, van Bokhoven H, Kleefstra T, Kahrizi K, Najmabadi H, Ropers HH, Delgado MR, Sirsi D, Golla S, Sommer A, Pietryga MP, Chung WK, Wynn J, Rohena L, Bernardo E, Hamlin D, Faux BM, Grange DK, Manwaring L, Tolmie J, Joss S, Cobben JM, Duijkers FAM, Goehringer JM, Challman TD, Hennig F, Fischer U, Grimme A, Suckow V, Musante L, Nicholl J, Shaw M, Lodh SP, Niu Z, Rosenfeld JA, Stankiewicz P, Jentsch TJ, Gecz J, Field M, Kalscheuer VM TITLE De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females. JOURNAL Mol Psychiatry 23:222-230 (2018) DOI:10.1038/mp.2016.135 PMID:26235985 (DDX3X) AUTHORS Snijders Blok L, Madsen E, Juusola J, Gilissen C, Baralle D, Reijnders MR, Venselaar H, Helsmoortel C, Cho MT, Hoischen A, Vissers LE, Koemans TS, Wissink-Lindhout W, Eichler EE, Romano C, Van Esch H, Stumpel C, Vreeburg M, Smeets E, Oberndorff K, van Bon BW, Shaw M, Gecz J, Haan E, Bienek M, Jensen C, Loeys BL, Van Dijck A, Innes AM, Racher H, Vermeer S, Di Donato N, Rump A, Tatton-Brown K, Parker MJ, Henderson A, Lynch SA, Fryer A, Ross A, Vasudevan P, Kini U, Newbury-Ecob R, Chandler K, Male A, Dijkstra S, Schieving J, Giltay J, van Gassen KL, Schuurs-Hoeijmakers J, Tan PL, Pediaditakis I, Haas SA, Retterer K, Reed P, Monaghan KG, Haverfield E, Natowicz M, Myers A, Kruer MC, Stein Q, Strauss KA, Brigatti KW, Keating K, Burton BK, Kim KH, Charrow J, Norman J, Foster-Barber A, Kline AD, Kimball A, Zackai E, Harr M, Fox J, McLaughlin J, Lindstrom K, Haude KM, van Roozendaal K, Brunner H, Chung WK, Kooy RF, Pfundt R, Kalscheuer V, Mehta SG, Katsanis N, Kleefstra T TITLE Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling. JOURNAL Am J Hum Genet 97:343-52 (2015) DOI:10.1016/j.ajhg.2015.07.004 PMID:25735484 (RLIM) AUTHORS Tonne E, Holdhus R, Stansberg C, Stray-Pedersen A, Petersen K, Brunner HG, Gilissen C, Hoischen A, Prescott T, Steen VM, Fiskerstrand T TITLE Syndromic X-linked intellectual disability segregating with a missense variant in RLIM. JOURNAL Eur J Hum Genet 23:1652-6 (2015) DOI:10.1038/ejhg.2015.30 PMID:23756445 (AP1S2) AUTHORS Cacciagli P, Desvignes JP, Girard N, Delepine M, Zelenika D, Lathrop M, Levy N, Ledbetter DH, Dobyns WB, Villard L TITLE AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome). JOURNAL Eur J Hum Genet 22:363-8 (2014) DOI:10.1038/ejhg.2013.135 PMID:12605440 (RBMX) AUTHORS Castro NH, dos Santos RC, Nelson R, Becak W, Hane B, Lindsey CJ, Lubs HA, Stevenson RE, Schwartz CE TITLE Shashi XLMR syndrome: report of a second family. JOURNAL Am J Med Genet A 118A:49-51 (2003) DOI:10.1002/ajmg.a.10888 PMID:11309367 (MECP2) AUTHORS Couvert P, Bienvenu T, Aquaviva C, Poirier K, Moraine C, Gendrot C, Verloes A, Andres C, Le Fevre AC, Souville I, Steffann J, des Portes V, Ropers HH, Yntema HG, Fryns JP, Briault S, Chelly J, Cherif B TITLE MECP2 is highly mutated in X-linked mental retardation. JOURNAL Hum Mol Genet 10:941-6 (2001) DOI:10.1093/hmg/10.9.941 PMID:17704778 (UPF3B) AUTHORS Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A, Vandeleur L, Smith R, Shoubridge C, Edkins S, Stevens C, O'Meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Hills K, Jones D, Mironenko T, Perry J, Varian J, West S, Widaa S, Teague J, Dicks E, Butler A, Menzies A, Richardson D, Jenkinson A, Shepherd R, Raine K, Moon J, Luo Y, Parnau J, Bhat SS, Gardner A, Corbett M, Brooks D, Thomas P, Parkinson-Lawrence E, Porteous ME, Warner JP, Sanderson T, Pearson P, Simensen RJ, Skinner C, Hoganson G, Superneau D, Wooster R, Bobrow M, Turner G, Stevenson RE, Schwartz CE, Futreal PA, Srivastava AK, Stratton MR, Gecz J TITLE Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. JOURNAL Nat Genet 39:1127-33 (2007) DOI:10.1038/ng2100 PMID:22814392 (CLIC2) AUTHORS Takano K, Liu D, Tarpey P, Gallant E, Lam A, Witham S, Alexov E, Chaubey A, Stevenson RE, Schwartz CE, Board PG, Dulhunty AF TITLE An X-linked channelopathy with cardiomegaly due to a CLIC2 mutation enhancing ryanodine receptor channel activity. JOURNAL Hum Mol Genet 21:4497-507 (2012) DOI:10.1093/hmg/dds292 PMID:26637982 (TAF1) AUTHORS O'Rawe JA, Wu Y, Dorfel MJ, Rope AF, Au PY, Parboosingh JS, Moon S, Kousi M, Kosma K, Smith CS, Tzetis M, Schuette JL, Hufnagel RB, Prada CE, Martinez F, Orellana C, Crain J, Caro-Llopis A, Oltra S, Monfort S, Jimenez-Barron LT, Swensen J, Ellingwood S, Smith R, Fang H, Ospina S, Stegmann S, Den Hollander N, Mittelman D, Highnam G, Robison R, Yang E, Faivre L, Roubertie A, Riviere JB, Monaghan KG, Wang K, Davis EE, Katsanis N, Kalscheuer VM, Wang EH, Metcalfe K, Kleefstra T, Innes AM, Kitsiou-Tzeli S, Rosello M, Keegan CE, Lyon GJ TITLE TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations. JOURNAL Am J Hum Genet 97:922-32 (2015) DOI:10.1016/j.ajhg.2015.11.005 PMID:26571461 (NONO) AUTHORS Mircsof D, Langouet M, Rio M, Moutton S, Siquier-Pernet K, Bole-Feysot C, Cagnard N, Nitschke P, Gaspar L, Znidaric M, Alibeu O, Fritz AK, Wolfer DP, Schroter A, Bosshard G, Rudin M, Koester C, Crestani F, Seebeck P, Boddaert N, Prescott K, Hines R, Moss SJ, Fritschy JM, Munnich A, Amiel J, Brown SA, Tyagarajan SK, Colleaux L TITLE Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects. JOURNAL Nat Neurosci 18:1731-6 (2015) DOI:10.1038/nn.4169 PMID:25316788 (RPL10) AUTHORS Brooks SS, Wall AL, Golzio C, Reid DW, Kondyles A, Willer JR, Botti C, Nicchitta CV, Katsanis N, Davis EE TITLE A novel ribosomopathy caused by dysfunction of RPL10 disrupts neurodevelopment and causes X-linked microcephaly in humans. JOURNAL Genetics 198:723-33 (2014) DOI:10.1534/genetics.114.168211 |