KEGG   DISEASE: X-linked intellectual developmental disorder
Entry
H00480                      Disease                                
Name
X-linked intellectual developmental disorder;
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 on physical examination, laboratory investigation and brain imaging.
Category
Mental and behavioural disorder
Brite
Human diseases in ICD-11 classification [BR:br08403]
 06 Mental, behavioural or neurodevelopmental disorders
  Neurodevelopmental disorders
   6A00  Disorders of intellectual development
    H00480  X-linked intellectual developmental disorder
Pathway-based classification of diseases [BR:br08402]
 Cellular process
  nt06523  Epigenetic regulation by Polycomb complexes
   H00480  X-linked intellectual developmental disorder
  nt06512  Chromosome cohesion and segregation
   H00480  X-linked intellectual developmental disorder
  nt06525  Ferroptosis
   H00480  X-linked intellectual developmental disorder
Pathway
hsa04810  Regulation of actin cytoskeleton
hsa04216  Ferroptosis
Network
nt06512 Chromosome cohesion and segregation
nt06523 Epigenetic regulation by Polycomb complexes
nt06525 Ferroptosis
Gene
(XLID1) IQSEC2 [HSA:23096] [KO:K12495]
(XLID3) HCFC1 [HSA:3054] [KO:K14966]
(XLID9) FTSJ1 [HSA:24140] [KO:K14864]
(XLID12) THOC2 [HSA:57187] [KO:K12879]
(XLID19) RPS6KA3 [HSA:6197] [KO:K04373]
(XLID21) IL1RAPL1 [HSA:11141] [KO:K05170]
(XLID29) ARX [HSA:170302] [KO:K09452]
(XLID30) PAK3 [HSA:5063] [KO:K05733]
(XLID41) GDI1 [HSA:2664] [KO:K17255]
(XLID58) TSPAN7 [HSA:7102] [KO:K06571]
(XLID63) ACSL4 [HSA:2182] [KO:K01897]
(XLID72) RAB39B [HSA:116442] [KO:K07925]
(XLID90) DLG3 [HSA:1741] [KO:K21098]
(XLID93) BRWD3 [HSA:254065] [KO:K11798]
(XLID96) SYP [HSA:6855]
(XLID97) ZNF711 [HSA:7552] [KO:K24376]
(XLID98) NEXMIF [HSA:340533] [KO:K25862]
(XLID99) USP9X [HSA:8239] [KO:K11840]
(XLID100) KIF4A [HSA:24137] [KO:K10395]
(XLID101) MID2 [HSA:11043] [KO:K10647]
(XLID103) KLHL15 [HSA:80311] [KO:K10452]
(XLID104) FRMPD4 [HSA:9758] [KO:K23956]
(XLID105) USP27X [HSA:389856] [KO:K11366]
(XLID106) OGT [HSA:8473] [KO:K09667]
(XLID107) STEEP1 [HSA:63932] [KO:K24996]
(XLID108) SLC9A7 [HSA:84679] [KO:K12041]
(XLID109) AFF2 [HSA:2334] [KO:K15194]
(XLID110) FGF13 [HSA:2258] [KO:K22413]
(XLID111) SLITRK2 [HSA:84631] [KO:K25833]
(XLID112) ZMYM3 [HSA:9203] [KO:K24675]
Other DBs
ICD-11: 6A00
ICD-10: F78.9
MeSH: C564490
OMIM: 309530 309541 309549 300957 300844 300143 300419 300558 300849 300436 300210 300387 300271 300850 300659 300802 300803 300912 300919 300923 300982 300983 300984 300997 301013 301024 309548 301095 301107 301111
Reference
  Authors
Renieri A, Pescucci C, Longo I, Ariani F, Mari F, Meloni I
  Title
Non-syndromic X-linked mental retardation: from a molecular to a clinical point of view.
  Journal
J Cell Physiol 204:8-20 (2005)
DOI:10.1002/jcp.20296
Reference
  Authors
Raymond FL
  Title
X linked mental retardation: a clinical guide.
  Journal
J Med Genet 43:193-200 (2006)
DOI:10.1136/jmg.2005.033043
Reference
  Authors
Ropers HH, Hamel BC
  Title
X-linked mental retardation.
  Journal
Nat Rev Genet 6:46-57 (2005)
DOI:10.1038/nrg1501
Reference
PMID:20473311 (XLID1)
  Authors
Shoubridge C, Tarpey PS, Abidi F, Ramsden SL, Rujirabanjerd S, Murphy JA, Boyle J, Shaw M, Gardner A, Proos A, Puusepp H, Raymond FL, Schwartz CE, Stevenson RE, Turner G, Field M, Walikonis RS, Harvey RJ, Hackett A, Futreal PA, Stratton MR, Gecz J
  Title
Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability.
  Journal
Nat Genet 42:486-8 (2010)
DOI:10.1038/ng.588
Reference
PMID:23000143 (XLID3)
  Authors
Huang L, Jolly LA, Willis-Owen S, Gardner A, Kumar R, Douglas E, Shoubridge C, Wieczorek D, Tzschach A, Cohen M, Hackett A, Field M, Froyen G, Hu H, Haas SA, Ropers HH, Kalscheuer VM, Corbett MA, Gecz J
  Title
A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability.
  Journal
Am J Hum Genet 91:694-702 (2012)
DOI:10.1016/j.ajhg.2012.08.011
Reference
PMID:15162322 (XLID9)
  Authors
Freude K, Hoffmann K, Jensen LR, Delatycki MB, des Portes V, Moser B, Hamel B, van Bokhoven H, Moraine C, Fryns JP, Chelly J, Gecz J, Lenzner S, Kalscheuer VM, Ropers HH
  Title
Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation.
  Journal
Am J Hum Genet 75:305-9 (2004)
DOI:10.1086/422507
Reference
PMID:26166480 (XLID12)
  Authors
Kumar R, Corbett MA, van Bon BW, Woenig JA, Weir L, Douglas E, Friend KL, Gardner A, Shaw M, Jolly LA, Tan C, Hunter MF, Hackett A, Field M, Palmer EE, Leffler M, Rogers C, Boyle J, Bienek M, Jensen C, Van Buggenhout G, Van Esch H, Hoffmann K, Raynaud M, Zhao H, Reed R, Hu H, Haas SA, Haan E, Kalscheuer VM, Gecz J
  Title
THOC2 Mutations Implicate mRNA-Export Pathway in X-Linked Intellectual Disability.
  Journal
Am J Hum Genet 97:302-10 (2015)
DOI:10.1016/j.ajhg.2015.05.021
Reference
PMID:10319851 (XLID19)
  Authors
Merienne K, Jacquot S, Pannetier S, Zeniou M, Bankier A, Gecz J, Mandel JL, Mulley J, Sassone-Corsi P, Hanauer A
  Title
A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation.
  Journal
Nat Genet 22:13-4 (1999)
DOI:10.1038/8719
Reference
PMID:10471494 (XLID21)
  Authors
Carrie A, Jun L, Bienvenu T, Vinet MC, McDonell N, Couvert P, Zemni R, Cardona A, Van Buggenhout G, Frints S, Hamel B, Moraine C, Ropers HH, Strom T, Howell GR, Whittaker A, Ross MT, Kahn A, Fryns JP, Beldjord C, Marynen P, Chelly J
  Title
A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation.
  Journal
Nat Genet 23:25-31 (1999)
DOI:10.1038/12623
Reference
PMID:11971879 (XLID29)
  Authors
Bienvenu T, Poirier K, Friocourt G, Bahi N, Beaumont D, Fauchereau F, Ben Jeema L, Zemni R, Vinet MC, Francis F, Couvert P, Gomot M, Moraine C, van Bokhoven H, Kalscheuer V, Frints S, Gecz J, Ohzaki K, Chaabouni H, Fryns JP, Desportes V, Beldjord C, Chelly J
  Title
ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation.
  Journal
Hum Mol Genet 11:981-91 (2002)
DOI:10.1093/hmg/11.8.981
Reference
PMID:9731525 (XLID30)
  Authors
Allen KM, Gleeson JG, Bagrodia S, Partington MW, MacMillan JC, Cerione RA, Mulley JC, Walsh CA
  Title
PAK3 mutation in nonsyndromic X-linked mental retardation.
  Journal
Nat Genet 20:25-30 (1998)
DOI:10.1038/1675
Reference
PMID:9620768 (XLID41)
  Authors
D'Adamo P, Menegon A, Lo Nigro C, Grasso M, Gulisano M, Tamanini F, Bienvenu T, Gedeon AK, Oostra B, Wu SK, Tandon A, Valtorta F, Balch WE, Chelly J, Toniolo D
  Title
Mutations in GDI1 are responsible for X-linked non-specific mental retardation.
  Journal
Nat Genet 19:134-9 (1998)
DOI:10.1038/487
Reference
PMID:10655063 (XLID58)
  Authors
Zemni R, Bienvenu T, Vinet MC, Sefiani A, Carrie A, Billuart P, McDonell N, Couvert P, Francis F, Chafey P, Fauchereau F, Friocourt G, des Portes V, Cardona A, Frints S, Meindl A, Brandau O, Ronce N, Moraine C, van Bokhoven H, Ropers HH, Sudbrak R, Kahn A, Fryns JP, Beldjord C, Chelly J
  Title
A new gene involved in X-linked mental retardation identified by analysis of an X;2 balanced translocation.
  Journal
Nat Genet 24:167-70 (2000)
DOI:10.1038/72829
Reference
PMID:11889465 (XLID63)
  Authors
Meloni I, Muscettola M, Raynaud M, Longo I, Bruttini M, Moizard MP, Gomot M, Chelly J, des Portes V, Fryns JP, Ropers HH, Magi B, Bellan C, Volpi N, Yntema HG, Lewis SE, Schaffer JE, Renieri A
  Title
FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation.
  Journal
Nat Genet 30:436-40 (2002)
DOI:10.1038/ng857
Reference
PMID:20159109 (XLID72)
  Authors
Giannandrea M, Bianchi V, Mignogna ML, Sirri A, Carrabino S, D'Elia E, Vecellio M, Russo S, Cogliati F, Larizza L, Ropers HH, Tzschach A, Kalscheuer V, Oehl-Jaschkowitz B, Skinner C, Schwartz CE, Gecz J, Van Esch H, Raynaud M, Chelly J, de Brouwer AP, Toniolo D, D'Adamo P
  Title
Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly.
  Journal
Am J Hum Genet 86:185-95 (2010)
DOI:10.1016/j.ajhg.2010.01.011
Reference
PMID:15185169 (XLID90)
  Authors
Tarpey P, Parnau J, Blow M, Woffendin H, Bignell G, Cox C, Cox J, Davies H, Edkins S, Holden S, Korny A, Mallya U, Moon J, O'Meara S, Parker A, Stephens P, Stevens C, Teague J, Donnelly A, Mangelsdorf M, Mulley J, Partington M, Turner G, Stevenson R, Schwartz C, Young I, Easton D, Bobrow M, Futreal PA, Stratton MR, Gecz J, Wooster R, Raymond FL
  Title
Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation.
  Journal
Am J Hum Genet 75:318-24 (2004)
DOI:10.1086/422703
Reference
PMID:17668385 (XLID93)
  Authors
Field M, Tarpey PS, Smith R, Edkins S, O'Meara S, Stevens C, Tofts C, Teague J, Butler A, Dicks E, Barthorpe S, Buck G, Cole J, Gray K, Halliday K, Hills K, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Varian J, West S, Widaa S, Mallya U, Wooster R, Moon J, Luo Y, Hughes H, Shaw M, Friend KL, Corbett M, Turner G, Partington M, Mulley J, Bobrow M, Schwartz C, Stevenson R, Gecz J, Stratton MR, Futreal PA, Raymond FL
  Title
Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly.
  Journal
Am J Hum Genet 81:367-74 (2007)
DOI:10.1086/520677
Reference
PMID:19377476 (XLID96 XLID97)
  Authors
Tarpey PS, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C, O'Meara S, Latimer C, Dicks E, Menzies A, Stephens P, Blow M, Greenman C, Xue Y, Tyler-Smith C, Thompson D, Gray K, Andrews J, Barthorpe S, Buck G, Cole J, Dunmore R, Jones D, Maddison M, Mironenko T, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Teague J, Butler A, Jenkinson A, Jia M, Richardson D, Shepherd R, Wooster R, Tejada MI, Martinez F, Carvill G, Goliath R, de Brouwer AP, van Bokhoven H, Van Esch H, Chelly J, Raynaud M, Ropers HH, Abidi FE, Srivastava AK, Cox J, Luo Y, Mallya U, Moon J, Parnau J, Mohammed S, Tolmie JL, Shoubridge C, Corbett M, Gardner A, Haan E, Rujirabanjerd S, Shaw M, Vandeleur L, Fullston T, Easton DF, Boyle J, Partington M, Hackett A, Field M, Skinner C, Stevenson RE, Bobrow M, Turner G, Schwartz CE, Gecz J, Raymond FL, Futreal PA, Stratton MR
  Title
A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation.
  Journal
Nat Genet 41:535-43 (2009)
DOI:10.1038/ng.367
Reference
PMID:23615299 (XLID98)
  Authors
Van Maldergem L, Hou Q, Kalscheuer VM, Rio M, Doco-Fenzy M, Medeira A, de Brouwer AP, Cabrol C, Haas SA, Cacciagli P, Moutton S, Landais E, Motte J, Colleaux L, Bonnet C, Villard L, Dupont J, Man HY
  Title
Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth.
  Journal
Hum Mol Genet 22:3306-14 (2013)
DOI:10.1093/hmg/ddt187
Reference
PMID:24607389 (XLID99)
  Authors
Homan CC, Kumar R, Nguyen LS, Haan E, Raymond FL, Abidi F, Raynaud M, Schwartz CE, Wood SA, Gecz J, Jolly LA
  Title
Mutations in USP9X are associated with X-linked intellectual disability and disrupt neuronal cell migration and growth.
  Journal
Am J Hum Genet 94:470-8 (2014)
DOI:10.1016/j.ajhg.2014.02.004
Reference
PMID:24812067 (XLID100)
  Authors
Willemsen MH, Ba W, Wissink-Lindhout WM, de Brouwer AP, Haas SA, Bienek M, Hu H, Vissers LE, van Bokhoven H, Kalscheuer V, Nadif Kasri N, Kleefstra T
  Title
Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function.
  Journal
J Med Genet 51:487-94 (2014)
DOI:10.1136/jmedgenet-2013-102182
Reference
PMID:24115387 (XLID101)
  Authors
Geetha TS, Michealraj KA, Kabra M, Kaur G, Juyal RC, Thelma BK
  Title
Targeted deep resequencing identifies MID2 mutation for X-linked intellectual disability with varied disease severity in a large kindred from India.
  Journal
Hum Mutat 35:41-4 (2014)
DOI:10.1002/humu.22453
Reference
PMID:24817631 (XLID103)
  Authors
Mignon-Ravix C, Cacciagli P, Choucair N, Popovici C, Missirian C, Milh M, Megarbane A, Busa T, Julia S, Girard N, Badens C, Sigaudy S, Philip N, Villard L
  Title
Intragenic rearrangements in X-linked intellectual deficiency: results of a-CGH in a series of 54 patients and identification of TRPC5 and KLHL15 as potential XLID genes.
  Journal
Am J Med Genet A 164A:1991-7 (2014)
DOI:10.1002/ajmg.a.36602
Reference
PMID:25644381 (XLID104 XLID105)
  Authors
Hu H, Haas SA, Chelly J, Van Esch H, Raynaud M, de Brouwer AP, Weinert S, Froyen G, Frints SG, Laumonnier F, Zemojtel T, Love MI, Richard H, Emde AK, Bienek M, Jensen C, Hambrock M, Fischer U, Langnick C, Feldkamp M, Wissink-Lindhout W, Lebrun N, Castelnau L, Rucci J, Montjean R, Dorseuil O, Billuart P, Stuhlmann T, Shaw M, Corbett MA, Gardner A, Willis-Owen S, Tan C, Friend KL, Belet S, van Roozendaal KE, Jimenez-Pocquet M, Moizard MP, Ronce N, Sun R, O'Keeffe S, Chenna R, van Bommel A, Goke J, Hackett A, Field M, Christie L, Boyle J, Haan E, Nelson J, Turner G, Baynam G, Gillessen-Kaesbach G, Muller U, Steinberger D, Budny B, Badura-Stronka M, Latos-Bielenska A, Ousager LB, Wieacker P, Rodriguez Criado G, Bondeson ML, Anneren G, Dufke A, Cohen M, Van Maldergem L, Vincent-Delorme C, Echenne B, Simon-Bouy B, Kleefstra T, Willemsen M, Fryns JP, Devriendt K, Ullmann R, Vingron M, Wrogemann K, Wienker TF, Tzschach A, van Bokhoven H, Gecz J, Jentsch TJ, Chen W, Ropers HH, Kalscheuer VM
  Title
X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.
  Journal
Mol Psychiatry 21:133-48 (2016)
DOI:10.1038/mp.2014.193
Reference
PMID:28302723 (XLID106)
  Authors
Vaidyanathan K, Niranjan T, Selvan N, Teo CF, May M, Patel S, Weatherly B, Skinner C, Opitz J, Carey J, Viskochil D, Gecz J, Shaw M, Peng Y, Alexov E, Wang T, Schwartz C, Wells L
  Title
Identification and characterization of a missense mutation in the O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
  Journal
J Biol Chem 292:8948-8963 (2017)
DOI:10.1074/jbc.M116.771030
Reference
PMID:29374277 (XLID107)
  Authors
Verkerk AJMH, Zeidler S, Breedveld G, Overbeek L, Huigh D, Koster L, van der Linde H, de Esch C, Severijnen LA, de Vries BBA, Swagemakers SMA, Willemsen R, Hoogeboom AJM, van der Spek PJ, Oostra BA
  Title
CXorf56, a dendritic neuronal protein, identified as a new candidate gene for X-linked intellectual disability.
  Journal
Eur J Hum Genet 26:552-560 (2018)
DOI:10.1038/s41431-017-0051-9
Reference
PMID:30335141 (XLID108)
  Authors
Khayat W, Hackett A, Shaw M, Ilie A, Dudding-Byth T, Kalscheuer VM, Christie L, Corbett MA, Juusola J, Friend KL, Kirmse BM, Gecz J, Field M, Orlowski J
  Title
A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
  Journal
Hum Mol Genet 28:598-614 (2019)
DOI:10.1093/hmg/ddy371
Reference
PMID:21739600 (XLID109)
  Authors
Stettner GM, Shoukier M, Hoger C, Brockmann K, Auber B
  Title
Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion.
  Journal
Am J Med Genet A 155A:2003-7 (2011)
DOI:10.1002/ajmg.a.34122
Reference
PMID:34184986 (XLID110)
  Authors
Pan X, Zhao J, Zhou Z, Chen J, Yang Z, Wu Y, Bai M, Jiao Y, Yang Y, Hu X, Cheng T, Lu Q, Wang B, Li CL, Lu YJ, Diao L, Zhong YQ, Pan J, Zhu J, Xiao HS, Qiu ZL, Li J, Wang Z, Hui J, Bao L, Zhang X
  Title
5'-UTR SNP of FGF13 causes translational defect and intellectual disability.
  Journal
Elife 10:63021 (2021)
DOI:10.7554/eLife.63021
Reference
PMID:35840571 (XLID111)
  Authors
El Chehadeh S, Han KA, Kim D, Jang G, Bakhtiari S, Lim D, Kim HY, Kim J, Kim H, Wynn J, Chung WK, Vitiello G, Cutcutache I, Page M, Gecz J, Harper K, Han AR, Kim HM, Wessels M, Bayat A, Jaen AF, Selicorni A, Maitz S, de Brouwer APM, Silfhout AV, Armstrong M, Symonds J, Kury S, Isidor B, Cogne B, Nizon M, Feger C, Muller J, Torti E, Grange DK, Willems M, Kruer MC, Ko J, Piton A, Um JW
  Title
SLITRK2 variants associated with neurodevelopmental disorders impair excitatory synaptic function and cognition in mice.
  Journal
Nat Commun 13:4112 (2022)
DOI:10.1038/s41467-022-31566-z
Reference
PMID:24721225 (XLID112)
  Authors
Philips AK, Siren A, Avela K, Somer M, Peippo M, Ahvenainen M, Doagu F, Arvio M, Kaariainen H, Van Esch H, Froyen G, Haas SA, Hu H, Kalscheuer VM, Jarvela I
  Title
X-exome sequencing in Finnish families with intellectual disability--four novel mutations and two novel syndromic phenotypes.
  Journal
Orphanet J Rare Dis 9:49 (2014)
DOI:10.1186/1750-1172-9-49

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