Genetics of Recessive Cognitive Disorders

Abstract

Intellectual disability (ID) is one of the most heterogeneous disorders, presenting two to three times more than any other disability. Recent estimates indicate that there are about 2000–3000 genes underlying ID. The X‐linked genes have been studied most extensively, contributing to approximately 10% of cases. However, autosomal genes make up the vast majority of genes, which is responsible for monogenic forms of ID. In Western populations, it appears that autosomal dominant (AD) disorders are more common than autosomal recessive (AR) disorders; however, when we move to the Middle East, this ratio shifts significantly and AR disorders are major players in the hereditary disease burden there. There are prevalent genes contributing to non‐syndromic autosomal recessive intellectual disability (NSARID) including TUSC3, ELP2 and MAN1B1; however, there is a paucity of ARID studies in many countries, particularly in the Middle East. Although many ARID genes have been identified in the last few years with advances in next‐generation sequencing, many of the genes responsible for ARID have not yet been identified, but it is expected that the novel genes will be determined in future.

Key Concepts

  • Neuro‐developmental disorders arise from central nervous system (CNS) dysfunction, leading to gradual and progressive cognition or movement impairment. ID is one of the most studied and explored conditions amongst neurodegenerative disorders
  • The majority of genes responsible for ID has an autosomal mode of inheritance

Keywords: cognitive disorders; intellectual disability; mental retardation; autosomal recessive; non‐syndromic; consanguinity; Middle East

Annex References

Abou Jamra R, Wohlfart S, Zweier M, et al. (2011) Homozygosity mapping in 64 Syrian consanguineous families with non‐specific intellectual disability reveals 11 novel loci and high heterogeneity. European Journal of Human Genetics 19 (11): 1161–1166.

Adrian K, Bernhard MK, Breitinger HG and Ogilvie A (2000) Expression of purinergic receptors (ionotropic P2X1‐7 and metabotropic P2Y1‐11) during myeloid differentiation of HL60 cells. Biochimica et Biophysica Acta 1492 (1): 127–138.

Agus DB, Gambhir SS, Pardridge WM, et al. (1997) Vitamin C crosses the blood–brain barrier in the oxidized form through the glucose transporters. The Journal of Clinical Investigation 100 (11): 2842–2848.

Ahmad M, Srinivasula SM, Wang L, et al. (1997) CRADD, a novel human apoptotic adaptor molecule for caspase‐2, and FasL/tumor necrosis factor receptor‐interacting protein RIP. Cancer Research 57 (4): 615–619.

Aikawa J, Grobe K, Tsujimoto M and Esko JD (2001) Multiple isozymes of heparan sulfate/heparin GlcNAc N‐deacetylase/GlcN N‐sulfotransferase. Structure and activity of the fourth member, NDST4. The Journal of Biological Chemistry 276 (8): 5876–5882.

Albig W, Ebentheuer J, Klobeck G, Kunz J and Doenecke D (1996) A solitary human H3 histone gene on chromosome 1. Human Genetics 97 (4): 486–491.

Baroni MG, Oelbaum RS, Pozzilli P, et al. (1992) Polymorphisms at the GLUT1 (HepG2) and GLUT4 (muscle/adipocyte) glucose transporter genes and non‐insulin‐dependent diabetes mellitus (NIDDM). Human Genetics 88 (5): 557–561.

Basel‐Vanagaite L, Attia R, Yahav M, et al. (2006) The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non‐syndromic mental retardation. Journal of Medical Genetics 43 (3): 203–210.

Benzing T, Yaffe MB, Arnould T, et al. (2000) 14‐3‐3 interacts with regulator of G protein signaling proteins and modulates their activity. The Journal of Biological Chemistry 275 (36): 28167–28172.

Caliskan M, Chong JX, Uricchio L, et al. (2011) Exome sequencing reveals a novel mutation for autosomal recessive non‐syndromic mental retardation in the TECR gene on chromosome 19p13. Human Molecular Genetics 20 (7): 1285–1289.

Carlsson Y, Schwendimann L, Vontell R, et al. (2011) Genetic inhibition of caspase‐2 reduces hypoxic‐ischemic and excitotoxic neonatal brain injury. Annals of Neurology 70 (5): 781–789.

Contractor A, Swanson G and Heinemann SF (2001) Kainate receptors are involved in short‐ and long‐term plasticity at mossy fiber synapses in the hippocampus. Neuron 29 (1): 209–216.

Dango S, Mosammaparast N, Sowa ME, et al. (2011) DNA unwinding by ASCC3 helicase is coupled to ALKBH3‐dependent DNA alkylation repair and cancer cell proliferation. Molecular Cell 44 (3): 373–384.

Fan G, Xiao L, Cheng L, et al. (2000) Targeted disruption of NDST‐1 gene leads to pulmonary hypoplasia and neonatal respiratory distress in mice. FEBS Letters 467 (1): 7–11.

Fisk JC, Zurita‐Lopez C, Sayegh J, et al. (2010) TbPRMT6 is a type I protein arginine methyltransferase that contributes to cytokinesis in Trypanosoma brucei. Eukaryotic Cell 9 (6): 866–877.

Garshasbi M, Hadavi V, Habibi H, et al. (2008) A defect in the TUSC3 gene is associated with autosomal recessive mental retardation. American Journal of Human Genetics 82 (5): 1158–1164.

Garshasbi M, Kahrizi K, Hosseini M, et al. (2011) A novel nonsense mutation in TUSC3 is responsible for non‐syndromic autosomal recessive mental retardation in a consanguineous Iranian family. American Journal of Medical Genetics Part A 155A (8): 1976–1980.

Girard F, Strausfeld U, Fernandez A and Lamb NJ (1991) Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell 67 (6): 1169–1179.

Gloerich J, Ruiter JP, van den Brink DM, et al. (2006) Peroxisomal trans‐2‐enoyl‐CoA reductase is involved in phytol degradation. FEBS Letters 580 (8): 2092–2096.

Gonzalez DS, Karaveg K, Vandersall‐Nairn AS, Lal A and Moremen KW (1999) Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn‐linked oligosaccharide biosynthesis. The Journal of Biological Chemistry 274 (30): 21375–21386.

Guillemot F, Lo LC, Johnson JE, et al. (1993) Mammalian achaete‐scute homolog 1 is required for the early development of olfactory and autonomic neurons. Cell 75 (3): 463–476.

Gustafson MP, Welcker M, Hwang HC and Clurman BE (2005) Zcchc8 is a glycogen synthase kinase‐3 substrate that interacts with RNA‐binding proteins. Biochemical and Biophysical Research Communications 338 (3): 1359–1367.

Hashimoto S, Boissel S, Zarhrate M, et al. (2011) MED23 mutation links intellectual disability to dysregulation of immediate early gene expression. Science 333 (6046): 1161–1163.

Hawkes NA, Otero G, Winkler GS, et al. (2002) Purification and characterization of the human elongator complex. The Journal of Biological Chemistry 277 (4): 3047–3052.

Hein L, Altman JD and Kobilka BK (1999) Two functionally distinct alpha2‐adrenergic receptors regulate sympathetic neurotransmission. Nature 402 (6758): 181–184.

Henglein B, Chenivesse X, Wang J, Eick D and Brechot C (1994) Structure and cell cycle‐regulated transcription of the human cyclin A gene. Proceedings of the National Academy of Sciences of the United States of America 91 (12): 5490–5494.

Higgins JJ, Hao J, Kosofsky BE and Rajadhyaksha AM (2008) Dysregulation of large‐conductance Ca2+−activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation. Neurogenetics 9 (3): 219–223.

Higgins JJ, Pucilowska J, Lombardi RQ and Rooney JP (2004) A mutation in a novel ATP‐dependent Lon protease gene in a kindred with mild mental retardation. Neurology 63 (10): 1927–1931.

Horton S, Meredith A, Richardson JA and Johnson JE (1999) Correct coordination of neuronal differentiation events in ventral forebrain requires the bHLH factor MASH1. Molecular and Cellular Neurosciences 14 (4–5): 355–369.

Hu H, Eggers K, Chen W, et al. (2011) ST3GAL3 mutations impair the development of higher cognitive functions. American Journal of Human Genetics 89 (3): 407–414.

Hu WH, Pendergast JS, Mo XM, et al. (2005) NIBP, a novel NIK and IKK(beta)‐binding protein that enhances NF‐(kappa)B activation. The Journal of Biological Chemistry 280 (32): 29233–29241.

Hurov KE, Cotta‐Ramusino C and Elledge SJ (2010) A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Genes & Development 24 (17): 1939–1950.

Ito T, Yang M and May WS (1999) RAX, a cellular activator for double‐stranded RNA‐dependent protein kinase during stress signaling. The Journal of Biological Chemistry 274 (22): 15427–15432.

Jung DJ, Sung HS, Goo YW, et al. (2002) Novel transcription coactivator complex containing activating signal cointegrator 1. Molecular and Cellular Biology 22 (14): 5203–5211.

Kakar N, Goebel I, Daud S, et al. (2012) A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly. European Journal of Medical Genetics 55 (12): 727–731.

Karaveg K, Siriwardena A, Tempel W, et al. (2005) Mechanism of class 1 (glycosylhydrolase family 47) {alpha}‐mannosidases involved in N‐glycan processing and endoplasmic reticulum quality control. The Journal of Biological Chemistry 280 (16): 16197–16207.

Kelly SM, Leung SW, Pak C, et al. (2014) A conserved role for the zinc finger polyadenosine RNA binding protein, ZC3H14, in control of poly(A) tail length. RNA (New York, N.Y.) 20 (5): 681–688.

Khan MA, Rafiq MA, Noor A, et al. (2011) A novel deletion mutation in the TUSC3 gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability. BMC Medical Genetics 12: 56.

Knobloch M, Braun SM, Zurkirchen L, et al. (2013) Metabolic control of adult neural stem cell activity by Fasn‐dependent lipogenesis. Nature 493 (7431): 226–230.

Lamkanfi M, D'Hondt K, Vande Walle L, et al. (2005) A novel caspase‐2 complex containing TRAF2 and RIP1. The Journal of Biological Chemistry 280 (8): 6923–6932.

Langouet M, Saadi A, Rieunier G, et al. (2013) Mutation in TTI2 reveals a role for triple T complex in human brain development. Human Mutation 34 (11): 1472–1476.

Lassus P, Opitz‐Araya X and Lazebnik Y (2002) Requirement for caspase‐2 in stress‐induced apoptosis before mitochondrial permeabilization. Science 297 (5585): 1352–1354.

Le Sourd F, Boulben S, Le Bouffant R, et al. (2006) eEF1B: at the dawn of the 21st century. Biochimica et Biophysica Acta 1759 (1–2): 13–31.

Lin Y, Ma W and Benchimol S (2000) Pidd, a new death‐domain‐containing protein, is induced by p53 and promotes apoptosis. Nature Genetics 26 (1): 122–127.

Liu J and Straby KB (2000) The human tRNA(m(2)(2)G(26))dimethyltransferase: functional expression and characterization of a cloned hTRM1 gene. Nucleic Acids Research 28 (18): 3445–3451.

Loddo S, Parisi V, Doccini V, et al. (2013) Homozygous deletion in TUSC3 causing syndromic intellectual disability: a new patient. American Journal of Medical Genetics Part A 161A (8): 2084–2087.

Marangi G, Leuzzi V, Manti F, et al. (2013) TRAPPC9‐related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype. European Journal of Human Genetics 21 (2): 229–232.

Matsuoka S, Ballif BA, Smogorzewska A, et al. (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316 (5828): 1160–1166.

Mir A, Kaufman L, Noor A, et al. (2009) Identification of mutations in TRAPPC9, which encodes the NIK‐ and IKK‐beta‐binding protein, in nonsyndromic autosomal‐recessive mental retardation. American Journal of Human Genetics 85 (6): 909–915.

Mitsui S, Osako Y, Yokoi F, et al. (2009) A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction. The European Journal of Neuroscience 30 (12): 2368–2378.

Mochida GH, Mahajnah M, Hill AD, et al. (2009) A truncating mutation of TRAPPC9 is associated with autosomal‐recessive intellectual disability and postnatal microcephaly. American Journal of Human Genetics 85 (6): 897–902.

Molinari F, Foulquier F, Tarpey PS, et al. (2008) Oligosaccharyltransferase‐subunit mutations in nonsyndromic mental retardation. American Journal of Human Genetics 82 (5): 1150–1157.

Molinari F, Rio M, Meskenaite V, et al. (2002) Truncating neurotrypsin mutation in autosomal recessive nonsyndromic mental retardation. Science 298 (5599): 1779–1781.

Montalbano J, Lui K, Sheikh MS and Huang Y (2009) Identification and characterization of RBEL1 subfamily of GTPases in the Ras superfamily involved in cell growth regulation. The Journal of Biological Chemistry 284 (27): 18129–18142.

Moon YA and Horton JD (2003) Identification of two mammalian reductases involved in the two‐carbon fatty acyl elongation cascade. The Journal of Biological Chemistry 278 (9): 7335–7343.

Motazacker MM, Rost BR, Hucho T, et al. (2007) A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. American Journal of Human Genetics 81 (4): 792–798.

Muncke N, Jung C, Rudiger H, et al. (2003) Missense mutations and gene interruption in PROSIT240, a novel TRAP240‐like gene, in patients with congenital heart defect (transposition of the great arteries). Circulation 108 (23): 2843–2850.

Najmabadi H, Hu H, Garshasbi M, et al. (2011) Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 478 (7367): 57–63.

Najmabadi H, Motazacker MM, Garshasbi M, et al. (2007) Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non‐syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. Human Genetics 121 (1): 43–48.

Nolan DK, Chen P, Das S, Ober C and Waggoner D (2008) Fine mapping of a locus for nonsyndromic mental retardation on chromosome 19p13. American Journal of Medical Genetics Part A 146A (11): 1414–1422.

Ober C, Abney M and McPeek MS (2001) The genetic dissection of complex traits in a founder population. American Journal of Human Genetics 69 (5): 1068–1079.

Pagano M, Pepperkok R, Verde F, Ansorge W and Draetta G (1992) Cyclin A is required at two points in the human cell cycle. The EMBO Journal 11 (3): 961–971.

Pak C, Garshasbi M, Kahrizi K, et al. (2011) Mutation of the conserved polyadenosine RNA binding protein, ZC3H14/dNab2, impairs neural function in Drosophila and humans. Proceedings of the National Academy of Sciences of the United States of America 108 (30): 12390–12395.

Paschen W, Blackstone CD, Huganir RL and Ross CA (1994a) Human GluR6 kainate receptor (GRIK2): molecular cloning, expression, polymorphism, and chromosomal assignment. Genomics 20 (3): 435–440.

Paschen W, Hedreen JC and Ross CA (1994b) RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain tissue. Journal of Neurochemistry 63 (5): 1596–1602.

Peters GA, Seachrist DD, Keri RA and Sen GC (2009) The double‐stranded RNA‐binding protein, PACT, is required for postnatal anterior pituitary proliferation. Proceedings of the National Academy of Sciences of the United States of America 106 (26): 10696–10701.

Philippe O, Rio M, Carioux A, et al. (2009) Combination of linkage mapping and microarray‐expression analysis identifies NF‐kappaB signaling defect as a cause of autosomal‐recessive mental retardation. American Journal of Human Genetics 85 (6): 903–908.

Puffenberger EG, Jinks RN, Sougnez C, et al. (2012) Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One 7 (1): e28936.

Rafiq MA, Kuss AW, Puettmann L, et al. (2011) Mutations in the alpha 1,2‐mannosidase gene, MAN1B1, cause autosomal‐recessive intellectual disability. American Journal of Human Genetics 89 (1): 176–182.

Ropers F, Derivery E, Hu H, et al. (2011) Identification of a novel candidate gene for non‐syndromic autosomal recessive intellectual disability: the WASH complex member SWIP. Human Molecular Genetics 20 (13): 2585–2590.

Ryu S, Zhou S, Ladurner AG and Tjian R (1999) The transcriptional cofactor complex CRSP is required for activity of the enhancer‐binding protein Sp1. Nature 397 (6718): 446–450.

Sasaki J, Kofuji S, Itoh R, et al. (2010) The PtdIns(3,4)P(2) phosphatase INPP4A is a suppressor of excitotoxic neuronal death. Nature 465 (7297): 497–501.

Sato S, Tomomori‐Sato C, Parmely TJ, et al. (2004) A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Molecular Cell 14 (5): 685–691.

Schmidt‐Ullrich R, Memet S, Lilienbaum A, et al. (1996) NF‐kappaB activity in transgenic mice: developmental regulation and tissue specificity. Development 122 (7): 2117–2128.

Shuey DJ, Betty M, Jones PG, Khawaja XZ and Cockett MI (1998) RGS7 attenuates signal transduction through the G(alpha q) family of heterotrimeric G proteins in mammalian cells. Journal of Neurochemistry 70 (5): 1964–1972.

Spychala J, Datta NS, Takabayashi K, et al. (1996) Cloning of human adenosine kinase cDNA: sequence similarity to microbial ribokinases and fructokinases. Proceedings of the National Academy of Sciences of the United States of America 93 (3): 1232–1237.

Stelzl U, Worm U, Lalowski M, et al. (2005) A human protein‐protein interaction network: a resource for annotating the proteome. Cell 122 (6): 957–968.

Tachiwana H, Osakabe A, Kimura H and Kurumizaka H (2008) Nucleosome formation with the testis‐specific histone H3 variant, H3t, by human nucleosome assembly proteins in vitro. Nucleic Acids Research 36 (7): 2208–2218.

Takai H, Xie Y, de Lange T and Pavletich NP (2010) Tel2 structure and function in the Hsp90‐dependent maturation of mTOR and ATR complexes. Genes & Development 24 (18): 2019–2030.

Tasaki T, Sohr R, Xia Z, et al. (2007) Biochemical and genetic studies of UBR3, a ubiquitin ligase with a function in olfactory and other sensory systems. The Journal of Biological Chemistry 282 (25): 18510–18520.

Tompkins V, Hagen J, Zediak VP and Quelle DE (2006) Identification of novel ARF binding proteins by two‐hybrid screening. Cell Cycle 5 (6): 641–646.

Tremblay LO and Herscovics A (1999) Cloning and expression of a specific human alpha 1,2‐mannosidase that trims Man9GlcNAc2 to Man8GlcNAc2 isomer B during N‐glycan biosynthesis. Glycobiology 9 (10): 1073–1078.

Tsang WY and Dynlacht BD (2008) Double identity of SCAPER: a substrate and regulator of cyclin A/Cdk2. Cell Cycle 7 (6): 702–705.

Yun K, Fischman S, Johnson J, et al. (2002) Modulation of the notch signaling by Mash1 and Dlx1/2 regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon. Development 129 (21): 5029–5040.

Zhu X, Zhou A, Dey A, et al. (2002) Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects. Proceedings of the National Academy of Sciences of the United States of America 99 (16): 10293–10298.

References

Abou Jamra R, Wohlfart S, Zweier M, et al. (2011) Homozygosity mapping in 64 Syrian consanguineous families with non‐specific intellectual disability reveals 11 novel loci and high heterogeneity. European Journal of Human Genetics 19 (11): 1161–1166.

Al‐Tawashi A, Jung SY, Liu D, Su B and Qin J (2012) Protein implicated in nonsyndromic mental retardation regulates protein kinase A (PKA) activity. The Journal of Biological Chemistry 287 (18): 14644–14658.

American Psychiatric Association (2000 Text Revision) Diagnostic and Statistical Manual of Mental Disorders, fourth edn. Washington: American Psychiatric Association.

Basel‐Vanagaite L (2007) Genetics of autosomal recessive non‐syndromic mental retardation: recent advances. Clinical Genetics 72 (3): 167–174.

Carlsson Y, Schwendimann L, Vontell R, et al. (2011) Genetic inhibition of caspase‐2 reduces hypoxic‐ischemic and excitotoxic neonatal brain injury. Annals of Neurology 70 (5): 781–789.

Coppede F, Mancuso M, Siciliano G, Migliore L and Murri L (2006) Genes and the environment in neurodegeneration. Bioscience Reports 26 (5): 341–367.

De Fusco M, Vago R, Striano P, et al. (2014) The alpha2B‐adrenergic receptor is mutant in cortical myoclonus and epilepsy. Annals of Neurology 75 (1): 77–87.

Diaz AL and Gleeson JG (2009) The molecular and genetic mechanisms of neocortex development. Clinics in Perinatology 36 (3): 503–512.

Ellison JW, Rosenfeld JA and Shaffer LG (2013) Genetic basis of intellectual disability. Annual Review of Medicine 64: 441–450.

Fisk JC, Zurita‐Lopez C, Sayegh J, et al. (2010) TbPRMT6 is a type I protein arginine methyltransferase that contributes to cytokinesis in Trypanosoma brucei. Eukaryotic Cell 9 (6): 866–877.

Freude K, Hoffmann K, Jensen LR, et al. (2004) Mutations in the FTSJ1 gene coding for a novel S‐adenosylmethionine‐binding protein cause nonsyndromic X‐linked mental retardation. American Journal of Human Genetics 75 (2): 305–309.

Garshasbi M, Hadavi V, Habibi H, et al. (2008) A defect in the TUSC3 gene is associated with autosomal recessive mental retardation. American Journal of Human Genetics 82 (5): 1158–1164.

Garshasbi M, Kahrizi K, Hosseini M, et al. (2011) A novel nonsense mutation in TUSC3 is responsible for non‐syndromic autosomal recessive mental retardation in a consanguineous Iranian family. American Journal of Medical Genetics Part A 155A (8): 1976–1980.

Garshasbi M, Motazacker MM, Kahrizi K, et al. (2006) SNP array‐based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly. Human Genetics 118 (6): 708–715.

Giannandrea M, Bianchi V, Mignogna ML, et al. (2010) Mutations in the small GTPase gene RAB39B are responsible for X‐linked mental retardation associated with autism, epilepsy, and macrocephaly. American Journal of Human Genetics 86 (2): 185–195.

Ginolhac A, Vilstrup J, Stenderup J, et al. (2012) Improving the performance of true single molecule sequencing for ancient DNA. BMC Genomics 13: 177.

Hamamy H (2012) Consanguineous marriages: preconception consultation in primary health care settings. Journal of Community Genetics 3 (3): 185–192.

Hashimoto S, Boissel S, Zarhrate M, et al. (2011) MED23 mutation links intellectual disability to dysregulation of immediate early gene expression. Science 333 (6046): 1161–1163.

Higgins JJ, Hao J, Kosofsky BE and Rajadhyaksha AM (2008) Dysregulation of large‐conductance Ca2+−activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation. Neurogenetics 9 (3): 219–223.

Hu H, Eggers K, Chen W, et al. (2011) ST3GAL3 mutations impair the development of higher cognitive functions. American Journal of Human Genetics 89 (3): 407–414.

Hurov KE, Cotta‐Ramusino C and Elledge SJ (2010) A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Genes & Development 24 (17): 1939–1950.

Karaveg K, Siriwardena A, Tempel W, et al. (2005) Mechanism of class 1 (glycosylhydrolase family 47) {alpha}‐mannosidases involved in N‐glycan processing and endoplasmic reticulum quality control. The Journal of Biological Chemistry 280 (16): 16197–16207.

Kaufman L, Ayub M and Vincent JB (2010) The genetic basis of non‐syndromic intellectual disability: a review. Journal of Neurodevelopmental Disorders 2 (4): 182–209.

Kelly SM, Leung SW, Pak C, et al. (2014) A conserved role for the zinc finger polyadenosine RNA binding protein, ZC3H14, in control of poly(A) tail length. RNA (New York, N.Y.) 20 (5): 681–688.

Knobloch M, Braun SM, Zurkirchen L, et al. (2013) Metabolic control of adult neural stem cell activity by Fasn‐dependent lipogenesis. Nature 493 (7431): 226–230.

Kuss AW, Garshasbi M, Kahrizi K, et al. (2011) Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots. Human Genetics 129 (2): 141–148.

La Rosa S, Marando A, Gatti G, et al. (2013) Achaete‐scute homolog 1 as a marker of poorly differentiated neuroendocrine carcinomas of different sites: a validation study using immunohistochemistry and quantitative real‐time polymerase chain reaction on 335 cases. Human Pathology 44 (7): 1391–1399.

Li T, Lytle N, Lan JQ, Sandau US and Boison D (2012) Local disruption of glial adenosine homeostasis in mice associates with focal electrographic seizures: a first step in epileptogenesis? Glia 60 (1): 83–95.

Liu P, Begley M, Michowski W, et al. (2014) Cell‐cycle‐regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature 508 (7497): 541–545.

Marangi G, Orteschi D, Vigevano F, et al. (2012) Expanding the spectrum of rearrangements involving chromosome 19: a mild phenotype associated with a 19p13.12‐p13.13 deletion. American Journal of Medical Genetics Part A 158A (4): 888–893.

Martin J, Cervero A, Mir P, et al. (2013) The impact of next‐generation sequencing technology on preimplantation genetic diagnosis and screening. Fertility and Sterility 99 (4): 1054–1061, e1053.

Matsuoka S, Ballif BA, Smogorzewska A, et al. (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316 (5828): 1160–1166.

Mitsui S, Osako Y, Yokoi F, et al. (2009) A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction. The European Journal of Neuroscience 30 (12): 2368–2378.

Molinari F, Foulquier F, Tarpey PS, et al. (2008) Oligosaccharyltransferase‐subunit mutations in nonsyndromic mental retardation. American Journal of Human Genetics 82 (5): 1150–1157.

Motazacker MM, Rost BR, Hucho T, et al. (2007) A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. American Journal of Human Genetics 81 (4): 792–798.

Musante L and Ropers HH (2014) Genetics of recessive cognitive disorders. Trends in Genetics 30 (1): 32–39.

Najmabadi H, Hu H, Garshasbi M, et al. (2011) Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 478 (7367): 57–63.

Najmabadi H, Motazacker MM, Garshasbi M, et al. (2007) Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non‐syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. Human Genetics 121 (1): 43–48.

Namavar Y, Barth PG, Kasher PR, et al. (2011) Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain 134 (Pt 1): 143–156.

Novarino G, Fenstermaker AG, Zaki MS, et al. (2014) Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science 343 (6170): 506–511.

Pak C, Garshasbi M, Kahrizi K, et al. (2011) Mutation of the conserved polyadenosine RNA binding protein, ZC3H14/dNab2, impairs neural function in Drosophila and humans. Proceedings of the National Academy of Sciences of the United States of America 108 (30): 12390–12395.

Peters GA, Seachrist DD, Keri RA and Sen GC (2009) The double‐stranded RNA‐binding protein, PACT, is required for postnatal anterior pituitary proliferation. Proceedings of the National Academy of Sciences of the United States of America 106 (26): 10696–10701.

Ropers F, Derivery E, Hu H, et al. (2011) Identification of a novel candidate gene for non‐syndromic autosomal recessive intellectual disability: the WASH complex member SWIP. Human Molecular Genetics 20 (13): 2585–2590.

Ropers HH (2010) Genetics of early onset cognitive impairment. Annual Review of Genomics and Human Genetics 11: 161–187.

Ropers HH and Hamel BC (2005) X‐linked mental retardation. Nature Reviews Genetics 6 (1): 46–57.

Saadat M, Ansari‐Lari M and Farhud DD (2004) Consanguineous marriage in Iran. Annals of Human Biology 31 (2): 263–269.

Sasaki J, Kofuji S, Itoh R, et al. (2010) The PtdIns(3,4)P(2) phosphatase INPP4A is a suppressor of excitotoxic neuronal death. Nature 465 (7297): 497–501.

Tachiwana H, Osakabe A, Kimura H and Kurumizaka H (2008) Nucleosome formation with the testis‐specific histone H3 variant, H3t, by human nucleosome assembly proteins in vitro. Nucleic Acids Research 36 (7): 2208–2218.

van Bokhoven H (2011) Genetic and epigenetic networks in intellectual disabilities. Annual Review of Genetics 45: 81–104.

Vissers LE, de Ligt J, Gilissen C, et al. (2010) A de novo paradigm for mental retardation. Nature Genetics 42 (12): 1109–1112.

Further Reading

Knight SJL (2010) Genetics of Mental Retardation: An Overview Encompassing Learning Disability and Intellectual Disability (Monographs in Human Genetics). Vol. 18. Oxford, UK: Oxford NIHR Biomedical Research Centre.

Le Hellard S and Steen VM (2014) Genetic architecture of cognitive traits. Scandinavian Journal of Psychology 55 (3): 255–262.

Wong Lee‐Jun C (2013) Next Generation Sequencing: Translation to Clinical Diagnostics. New York Heidelberg Dordrecht London: Springer.

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Kahrizi, Kimia, and Najmabadi, Hossein(Mar 2015) Genetics of Recessive Cognitive Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025835]