X-linked mental retardation

X-linked mental retardation (XLMR) is an inherited condition that causes failure to develop cognitive abilities because of mutations in several genes on the X chromosome. XLMR is subdivided into syndromic and non-syndromic forms (NS-XLMR), depending on whether further abnormalities are found on physical examination, laboratory investigation and brain imaging. The majority of genes that are mutated in NS-XLMR encode proteins are involved in three distinct pathways: Rho GTPases pathway modulating neuronal differentiation and synaptic plasticity; Rab GTPases pathway regulating synaptic vesicle cycling; gene expression regulation.

Mental and behavioural disorder

(MRX1/78) IQSEC2 [HSA:23096] [KO:K12495]
(MRX3) HCFC1 [HSA:3054] [KO:K14966]
(MRX9/44) FTSJ1 [HSA:24140] [KO:K14864]
(MRX12/35) THOC2 [HSA:57187] [KO:K12879]
(MRX19) RPS6KA3 [HSA:6197] [KO:K04373]
(MRX21/34) IL1RAPL1 [HSA:11141] [KO:K05170]
(MRX29s) ARX [HSA:170302] [KO:K09452]
(MRX30/47) PAK3 [HSA:5063] [KO:K05733]
(MRX41) GDI1 [HSA:2664] [KO:K17255]
(MRX46) ARHGEF6 [HSA:9459] [KO:K05729]
(MRX49/15) CLCN4 [HSA:1183] [KO:K05012]
(MRX58) TSPAN7 [HSA:7102] [KO:K06571]
(MRX61) RLIM [HSA:51132] [KO:K16271]
(MRX63) ACSL4 [HSA:2182] [KO:K01897]
(MRX72) RAB39B [HSA:116442] [KO:K07925]
(MRX90) DLG3 [HSA:1741] [KO:K21098]
(MRX91) ZDHHC15 [HSA:158866] [KO:K20028]
(MRX93) BRWD3 [HSA:254065] [KO:K11798]
(MRX96) SYP [HSA:6855]
(MRX97) ZNF711 [HSA:7552] [KO:K24376]
(MRX98) NEXMIF [HSA:340533]
(MRX99) USP9X [HSA:8239] [KO:K11840]
(MRX100) KIF4A [HSA:24137] [KO:K10395]
(MRX101) MID2 [HSA:11043] [KO:K10647]
(MRX102) DDX3X [HSA:1654] [KO:K11594]
(MRX103) KLHL15 [HSA:80311] [KO:K10452]
(MRX104) FRMPD4 [HSA:9758] [KO:K23956]
(MRX105) USP27X [HSA:389856] [KO:K11366]
(MRX106) OGT [HSA:8473] [KO:K09667]
(MRX107) CXorf56 [HSA:63932]
(MRX108) SLC9A7 [HSA:84679] [KO:K12041]

PMID:15690397

Renieri A, Pescucci C, Longo I, Ariani F, Mari F, Meloni I

Non-syndromic X-linked mental retardation: from a molecular to a clinical point of view.

J Cell Physiol 204:8-20 (2005)
DOI:10.1002/jcp.20296

PMID:16118346

Raymond FL

X linked mental retardation: a clinical guide.

J Med Genet 43:193-200 (2006)
DOI:10.1136/jmg.2005.033043

PMID:15630421

Ropers HH, Hamel BC

X-linked mental retardation.

Nat Rev Genet 6:46-57 (2005)
DOI:10.1038/nrg1501

PMID:18455129

Molinari F, Foulquier F, Tarpey PS, Morelle W, Boissel S, Teague J, Edkins S, Futreal PA, Stratton MR, Turner G, Matthijs G, Gecz J, Munnich A, Colleaux L

Oligosaccharyltransferase-subunit mutations in nonsyndromic mental retardation.

Am J Hum Genet 82:1150-7 (2008)
DOI:10.1016/j.ajhg.2008.03.021

PMID:20473311

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

Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability.

Nat Genet 42:486-8 (2010)
DOI:10.1038/ng.588

PMID:25644381

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

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.

Mol Psychiatry 21:133-48 (2016)
DOI:10.1038/mp.2014.193

PMID:23000143

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

A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability.

Am J Hum Genet 91:694-702 (2012)
DOI:10.1016/j.ajhg.2012.08.011

PMID:9415477

Claes S, Vogels A, Holvoet M, Devriendt K, Raeymaekers P, Cassiman JJ, Fryns JP

Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3-p22.2 (MRX49) and Xp11.3-p11.21 (MRX50).

Am J Med Genet 73:474-9 (1997)
DOI:10.1002/(SICI)1096-8628(19971231)73:4<474::AID-AJMG18>3.0.CO;2-O

PMID:27993705

van der Werf IM, Van Dijck A, Reyniers E, Helsmoortel C, Kumar AA, Kalscheuer VM, de Brouwer AP, Kleefstra T, van Bokhoven H, Mortier G, Janssens S, Vandeweyer G, Kooy RF

Mutations in two large pedigrees highlight the role of ZNF711 in X-linked intellectual disability.

Gene 605:92-98 (2017)
DOI:10.1016/j.gene.2016.12.013

PMID:28302723

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

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.

J Biol Chem 292:8948-8963 (2017)
DOI:10.1074/jbc.M116.771030