Haploinsufficiency of the HIRA gene located in the 22q11 deletion syndrome region is associated with abnormal neurodevelopment and impaired dendritic outgrowth.
Animals
Base Sequence
Cell Cycle Proteins
/ antagonists & inhibitors
Child
Child, Preschool
Corpus Callosum
/ metabolism
DiGeorge Syndrome
/ genetics
Female
Fornix, Brain
/ metabolism
Gene Expression
Haploinsufficiency
Heterozygote
Hippocampus
/ metabolism
Histone Chaperones
/ antagonists & inhibitors
Humans
Mice
Neurodevelopmental Disorders
/ genetics
Neurogenesis
/ genetics
Neuronal Plasticity
/ genetics
Neurons
/ metabolism
Primary Cell Culture
RNA, Small Interfering
/ genetics
Transcription Factors
/ antagonists & inhibitors
Journal
Human genetics
ISSN: 1432-1203
Titre abrégé: Hum Genet
Pays: Germany
ID NLM: 7613873
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
17
07
2020
accepted:
22
12
2020
pubmed:
9
1
2021
medline:
13
5
2021
entrez:
8
1
2021
Statut:
ppublish
Résumé
The 22q11.2 deletion syndrome (22q11DS) is associated with a wide spectrum of cognitive and psychiatric symptoms. Despite the considerable work performed over the past 20 years, the genetic etiology of the neurodevelopmental phenotype remains speculative. Here, we report de novo heterozygous truncating variants in the HIRA (Histone cell cycle regulation defective, S. Cerevisiae, homolog of, A) gene associated with a neurodevelopmental disorder in two unrelated patients. HIRA is located within the commonly deleted region of the 22q11DS and encodes a histone chaperone that regulates neural progenitor proliferation and neurogenesis, and that belongs to the WD40 Repeat (WDR) protein family involved in brain development and neuronal connectivity. To address the specific impact of HIRA haploinsufficiency in the neurodevelopmental phenotype of 22q11DS, we combined Hira knock-down strategies in developing mouse primary hippocampal neurons, and the direct study of brains from heterozygous Hira
Identifiants
pubmed: 33417013
doi: 10.1007/s00439-020-02252-1
pii: 10.1007/s00439-020-02252-1
doi:
Substances chimiques
Cell Cycle Proteins
0
HIRA protein, human
0
Hira protein, mouse
0
Histone Chaperones
0
RNA, Small Interfering
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
885-896Références
Andrade DM, Krings T, Chow EWC, Kiehl T-R, Bassett AS (2013) Hippocampal malrotation is associated with chromosome 22q11.2 microdeletion. Can J Neurol Sci 40:652–656. https://doi.org/10.1017/s0317167100014876
doi: 10.1017/s0317167100014876
pubmed: 23968937
pmcid: 4459860
Bassett AS, Caluseriu O, Weksberg R, Young DA, Chow EWC (2007) Catechol-O-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome. Biol Psychiatry 61:1135–1140. https://doi.org/10.1016/j.biopsych.2006.07.038
doi: 10.1016/j.biopsych.2006.07.038
pubmed: 17217925
pmcid: 3142270
Beemer FA, Emanuel BS, Kahn RS, van Engeland H, Kemner C (2009) Proline affects brain function in 22q11DS children with the low activity COMT 158 allele. Neuropsychopharmacology 34:739–746. https://doi.org/10.1038/npp.2008.132
doi: 10.1038/npp.2008.132
pubmed: 18769474
Bohm LA, Zhou TC, Mingo TJ, Dugan SL, Patterson RJ, Sidman JD, Roby BB (2017) Neuroradiographic findings in 22q11.2 deletion syndrome. Am J Med Genet A 173:2158–2165. https://doi.org/10.1002/ajmg.a.38304
doi: 10.1002/ajmg.a.38304
pubmed: 28577347
Bruining H, de Sonneville L, Swaab H, de Jonge M, Kas M, van Engeland H, Vorstman J (2010) Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. PLoS ONE 5:e10887. https://doi.org/10.1371/journal.pone.0010887
doi: 10.1371/journal.pone.0010887
pubmed: 20526357
pmcid: 2878316
Collins SC, Wagner C, Gagliardi L, Kretz PF, Fischer MC, Kessler P, Kannan M, Yalcin B (2018) A method for parasagittal sectioning for neuroanatomical quantification of brain structures in the adult mouse. Curr Protoc Mouse Biol 8:e48. https://doi.org/10.1002/cpmo.48
doi: 10.1002/cpmo.48
pubmed: 29944194
De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton PF, Brownfeld JM, Cai J, Campbell NG, Carracedo A, Chahrour MH, Chiocchetti AG, Coon H, Crawford EL, Curran SR, Dawson G, Duketis E, Fernandez BA, Gallagher L, Geller E, Guter SJ, Hill RS, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck SM, Kolevzon A, Lee I, Lei I, Lei J, Lehtimäki T, Lin CF, Ma’ayan A, Marshall CR, McInnes AL, Neale B, Owen MJ, Ozaki N, Parellada M, Parr JR, Purcell S, Puura K, Rajagopalan D, Rehnström K, Reichenberg A, Sabo A, Sachse M, Sanders SJ, Schafer C, Schulte-Rüther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss LA, Willsey AJ, Yu TW, Yuen RK, Cook EH, Freitag CM, Gill M, Hultman CM, Lehner T, Palotie A, Schellenberg GD, Sklar P, State MW, Sutcliffe JS, Walsh CA, Scherer SW, Zwick ME, Barett JC, Cutler DJ, Roeder K, Devlin B, Daly MJ, Buxbaum JD, DDD Study; Homozygosity Mapping Collaborative for Autism; UK10K Consortium (2014) Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515:209–215. https://doi.org/10.1038/nature13772
doi: 10.1038/nature13772
pubmed: 25363760
pmcid: 4402723
De Smedt B, Devriendt K, Fryns J-P, Vogels A, Gewillig M, Swillen A (2007) Intellectual abilities in a large sample of children with velo-cardio-facial syndrome: an update. J Intellect Disabil Res 51:666–670. https://doi.org/10.1111/j.1365-2788.2007.00955.x
doi: 10.1111/j.1365-2788.2007.00955.x
pubmed: 17845235
Deciphering Developmental Disorders Study (2017) Prevalence and architecture of de novo mutations in developmental disorders. Nature 542:433–438. https://doi.org/10.1038/nature21062
doi: 10.1038/nature21062
Dilg D, Saleh RN, Phelps SE, Rose Y, Dupays L, Murphy C, Mohun T, Anderson RH, Scambler PJ, Chapgier AL (2016) HIRA is required for heart development and directly regulates Tnni2 and Tnnt3. PLoS ONE 11:e0161096. https://doi.org/10.1371/journal.pone.0161096
doi: 10.1371/journal.pone.0161096
pubmed: 27518902
pmcid: 4982693
Fénelon K, Xu B, Lai CS, Mukai J, Markx S, Stark KL, Hsu PK, Gan WB, Fischbach GD, MacDermott AB, Karayiorgou M, Gogos JA (2013) The pattern of cortical dysfunction in a mouse model of a schizophrenia-related microdeletion. J Neurosci 33:14825–14839. https://doi.org/10.1523/JNEUROSCI.1611-13.2013
doi: 10.1523/JNEUROSCI.1611-13.2013
pubmed: 24027283
pmcid: 3771024
Fine SE, Weissman A, Gerdes M, Pinto-Martin J, Zackai EH, McDonald-McGinn DM, Emanuel BS (2005) Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. J Autism Dev Disord 35:461–470. https://doi.org/10.1007/s10803-005-5036-9
doi: 10.1007/s10803-005-5036-9
pubmed: 16134031
pmcid: 2814423
Forsyth JK, Nachun D, Gandal MJ, Geschwind DH, Anderson AE, Coppola G, Bearden CE (2020) Synaptic and gene regulatory mechanisms in schizophrenia, autism, and 22q11.2 CNV mediated risk for neuropsychiatric disorders. Biol Psychiatry 87:150–163. https://doi.org/10.1016/j.biopsych.2019.06.029
doi: 10.1016/j.biopsych.2019.06.029
pubmed: 31500805
Goodman BK, Rutberg J, Lin WW, Pulver AE, Thomas GH (2000) Hyperprolinaemia in patients with deletion (22)(q11.2) syndrome. J Inherit Metab Dis 23:847–848. https://doi.org/10.1023/a:1026773005303
doi: 10.1023/a:1026773005303
pubmed: 11196113
Gothelf D, Schneider M, Green T, Debbané M, Frisch A, Glaser B, Zilkha H, Schaer M, Weizman A, Eliez S (2013) Risk factors and the evolution of psychosis in 22q11.2 deletion syndrome: a longitudinal 2-site study. J Am Acad Child Adolesc Psychiatry 52:1192-1203.e3. https://doi.org/10.1016/j.jaac.2013.08.008
doi: 10.1016/j.jaac.2013.08.008
pubmed: 24157393
Jacquet H, Raux G, Thibaut F, Hecketsweiler B, Houy E, Demilly C, Haouzir S, Allio G, Fouldrin G, Drouin V, Bou J, Petit M, Campion D, Frébourg T (2002) PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. Hum Mol Genet 11:2243–2249. https://doi.org/10.1093/hmg/11.19.2243
doi: 10.1093/hmg/11.19.2243
pubmed: 12217952
Kannan M, Bayam E, Wagner C, Rinaldi B, Kretz PF, Tilly P, Roos M, McGillewie L, Bär S, Minocha S, Chevalier C, Po C, Chelly J, Mandel JL, Borgatti R, Piton A, Kinnear C, Loos B, Adams DJ, Hérault Y, Collins SC, Friant S, Godin JD, Yalcin B, Sanger Mouse Genetics Project (2017) WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy. Proc Natl Acad Sci USA 114:E9308–E9317. https://doi.org/10.1073/pnas.1713625114
doi: 10.1073/pnas.1713625114
pubmed: 29078390
Kates WR, Burnette CP, Bessette BA, Folley BS, Strunge L, Jabs EW, Pearlson GD (2004) Frontal and caudate alterations in velocardiofacial syndrome (deletion at chromosome 22q11.2). J Child Neurol 19:337–342. https://doi.org/10.1177/088307380401900506
doi: 10.1177/088307380401900506
pubmed: 15224707
Kummeling J, Stremmelaar DE, Raun N, Reijnders MRF, Willemsen MH, Ruiterkamp-Versteeg M, Schepens M, Man CCO, Gilissen C, Cho MT, McWalter K, Sinnema M, Wheless JW, Simon MEH, Genetti CA, Casey AM, Terhal PA, van der Smagt JJ, van Gassen KLI, Joset P, Bahr A, Steindl K, Rauch A, Keller E, Raas-Rothschild A, Koolen DA, Agrawal PB, Hoffman TL, Powell-Hamilton NN, Thiffault I, Engleman K, Zhou D, Bodamer O, Hoefele J, Riedhammer KM, Schwaibold EMC, Tasic V, Schubert D, Top D, Pfundt R, Higgs MR, Kramer JM, Kleefstra T (2020) Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome. Mol Psychiatry. https://doi.org/10.1038/s41380-020-0725-5
doi: 10.1038/s41380-020-0725-5
pubmed: 32346159
Li Y, Jiao J (2017) Histone chaperone HIRA regulates neural progenitor cell proliferation and neurogenesis via β-catenin. J Cell Biol 216:1975–1992. https://doi.org/10.1083/jcb.201610014
doi: 10.1083/jcb.201610014
pubmed: 28515277
pmcid: 5496612
Meechan DW, Maynard TM, Tucker ES, Fernandez A, Karpinski BA, Rothblat LA, LaMantia A-S (2015) Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development. Prog Neurobiol 130:1–28. https://doi.org/10.1016/j.pneurobio.2015.03.004
doi: 10.1016/j.pneurobio.2015.03.004
pubmed: 25866365
pmcid: 5019355
Moutin E, Nikonenko I, Stefanelli T, Wirth A, Ponimaskin E, De Roo M, Muller D (2017) Palmitoylation of cdc42 promotes spine stabilization and rescues spine density deficit in a mouse model of 22q11.2 deletion syndrome. Cereb Cortex 27:3618–3629. https://doi.org/10.1093/cercor/bhw183
doi: 10.1093/cercor/bhw183
pubmed: 27365300
Mukai J, Dhilla A, Drew LJ, Stark KL, Cao L, MacDermott AB, Karayiorgou M, Gogos JA (2008) Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nat Neurosci 11:1302–1310. https://doi.org/10.1038/nn.2204
doi: 10.1038/nn.2204
pubmed: 18836441
pmcid: 2756760
Mukai J, Tamura M, Fénelon K, Rosen AM, Spellman TJ, Kang R, MacDermott AB, Karayiorgou M, Gordon JA, Gogos JA (2015) Molecular substrates of altered axonal growth and brain connectivity in a mouse model of schizophrenia. Neuron 86:680–695. https://doi.org/10.1016/j.neuron.2015.04.003
doi: 10.1016/j.neuron.2015.04.003
pubmed: 25913858
pmcid: 4603834
Nashun B, Hill PW, Smallwood SA, Dharmalingam G, Amouroux R, Clark SJ, Sharma V, Ndjetehe E, Pelczar P, Festenstein RJ, Kelsey G, Hajkova P (2015) Continuous histone replacement by hira is essential for normal transcriptional regulation and de novo dna methylation during mouse oogenesis. Mol Cell 60:611–625. https://doi.org/10.1016/j.molcel.2015.10.010
doi: 10.1016/j.molcel.2015.10.010
pubmed: 26549683
pmcid: 4672152
Paronett EM, Meechan DW, Karpinski BA, LaMantia A-S, Maynard TM (2015) Ranbp1, deleted in DiGeorge/22q11.2 deletion syndrome, is a microcephaly gene that selectively disrupts layer 2/3 cortical projection neuron generation. Cereb Cortex 25:3977–3993. https://doi.org/10.1093/cercor/bhu285
doi: 10.1093/cercor/bhu285
pubmed: 25452572
Philip N, Bassett A (2011) Cognitive, behavioural and psychiatric phenotype in 22q11.2 deletion syndrome. Behav Genet 41:403–412. https://doi.org/10.1007/s10519-011-9468-z
doi: 10.1007/s10519-011-9468-z
pubmed: 21573985
pmcid: 3139630
Rauch A, Hoyer J, Guth S, Zweier C, Kraus C, Becker C, Zenker M, Hüffmeier U, Thiel C, Rüschendorf F, Nürnberg P, Reis A, Trautmann U (2006) Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet A 140:2063–2074. https://doi.org/10.1002/ajmg.a.31416
doi: 10.1002/ajmg.a.31416
pubmed: 16917849
Raux G, Bumsel E, Hecketsweiler B, van Amelsvoort T, Zinkstok J, Manouvrier-Hanu S, Fantini C, Brévière GM, Di Rosa G, Pustorino G, Vogels A, Swillen A, Legallic S, Bou J, Opolczynski G, Drouin-Garraud V, Lemarchand M, Philip N, Gérard-Desplanches A, Carlier M, Philippe A, Nolen MC, Heron D, Sarda P, Lacombe D, Coizet C, Alembik Y, Layet V, Afenjar A, Hannequin D, Demily C, Petit M, Thibaut F, Frebourg T, Campion D (2007) Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. Hum Mol Genet 16:83–91. https://doi.org/10.1093/hmg/ddl443
doi: 10.1093/hmg/ddl443
pubmed: 17135275
Roberts C, Sutherland HF, Farmer H, Kimber W, Halford S, Carey A, Brickman JM, Wynshaw-Boris A, Scambler PJ (2002) Targeted mutagenesis of the hira gene results in gastrulation defects and patterning abnormalities of mesoendodermal derivatives prior to early embryonic lethality. Mol Cell Biol 22:2318–2328. https://doi.org/10.1128/mcb.22.7.2318-2328.2002
doi: 10.1128/mcb.22.7.2318-2328.2002
pubmed: 11884616
pmcid: 133693
Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, Schuffenhauer S, Oechsler H, Belohradsky B, Prieur M, Aurias A, Raymond FL, Clayton-Smith J, Hatchwell E, McKeown C, Beemer FA, Dallapiccola B, Novelli G, Hurst JA, Ignatius J, Green AJ, Winter RM, Brueton L, Brøndum-Nielsen K, Scambler PJ (1997) Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 34:798–804. https://doi.org/10.1136/jmg.34.10.798
doi: 10.1136/jmg.34.10.798
pubmed: 9350810
pmcid: 1051084
Schneider M, Debbané M, Bassett AS, Chow EW, Fung WL, van den Bree M, Owen M, Murphy KC, Niarchou M, Kates WR, Antshel KM, Fremont W, McDonald-McGinn DM, Gur RE, Zackai EH, Vorstman J, Duijff SN, Klaassen PW, Swillen A, Gothelf D, Green T, Weizman A, Van Amelsvoort T, Evers L, Boot E, Shashi V, Hooper SR, Bearden CE, Jalbrzikowski M, Armando M, Vicari S, Murphy DG, Ousley O, Campbell LE, Simon TJ, Eliez S, International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome (2014) Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the international consortium on brain and behavior in 22q11.2 deletion syndrome. Am J Psychiatry 171:627–639. https://doi.org/10.1176/appi.ajp.2013.13070864
doi: 10.1176/appi.ajp.2013.13070864
pubmed: 24577245
pmcid: 4285461
Simon TJ, Ding L, Bish JP, McDonald-McGinn DM, Zackai EH, Gee J (2005) Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study. NeuroImage 25:169–180. https://doi.org/10.1016/j.neuroimage.2004.11.018
doi: 10.1016/j.neuroimage.2004.11.018
pubmed: 15734353
Singh T, Kurki MI, Curtis D, Purcell SM, Crooks L, McRae J, Suvisaari J, Chheda H, Blackwood D, Breen G, Pietiläinen O, Gerety SS, Ayub M, Blyth M, Cole T, Collier D, Coomber EL, Craddock N, Daly MJ, Danesh J, DiForti M, Foster A, Freimer NB, Geschwind D, Johnstone M, Joss S, Kirov G, Körkkö J, Kuismin O, Holmans P, Hultman CM, Iyegbe C, Lönnqvist J, Männikkö M, McCarroll SA, McGuffin P, McIntosh AM, McQuillin A, Moilanen JS, Moore C, Murray RM, Newbury-Ecob R, Ouwehand W, Paunio T, Prigmore E, Rees E, Roberts D, Sambrook J, Sklar P, St Clair D, Veijola J, Walters JT, Williams H, Sullivan PF, Hurles ME, O’Donovan MC, Palotie A, Owen MJ, Barrett JC, Swedish Schizophrenia Study; INTERVAL Study; DDD Study; UK10 K Consortium (2016) Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nat Neurosci 19:571–577. https://doi.org/10.1038/nn.4267
doi: 10.1038/nn.4267
pubmed: 26974950
pmcid: 6689268
Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011) A conditional knockout resource for the genome-wide study of mouse gene function. Nature 474:337–342. https://doi.org/10.1038/nature10163
doi: 10.1038/nature10163
pubmed: 21677750
pmcid: 3572410
Swillen A, Devriendt K, Legius E, Eyskens B, Dumoulin M, Gewillig M, Fryns JP (1997) Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS. J Med Genet 34:453–458. https://doi.org/10.1136/jmg.34.6.453
doi: 10.1136/jmg.34.6.453
pubmed: 9192263
pmcid: 1050966
Valenzuela N, Soibam B, Li L, Wang J, Byers LA, Liu Y, Schwartz RJ, Stewart MD (2017) HIRA deficiency in muscle fibers causes hypertrophy and susceptibility to oxidative stress. J Cell Sci 130:2551–2563. https://doi.org/10.1242/jcs.200642
doi: 10.1242/jcs.200642
pubmed: 28600325
Vorstman JAS, Morcus MEJ, Duijff SN, Klaassen PWJ, Heineman-de Boer JA, Beemer FA, Swaab H, Kahn RS, van Engeland H (2006) The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry 45:1104–1113. https://doi.org/10.1097/01.chi.0000228131.56956.c1
doi: 10.1097/01.chi.0000228131.56956.c1
pubmed: 16926618
Vorstman JA, Turetsky BI, Sijmens-Morcus ME, de Sain MG, Dorland B, Sprong M, Rappaport EF, Beemer FA, Emanuel BS, Kahn RS, van Engeland H, Kemner C (2009) Proline affects brain function in 22q11DS children with the low activity COMT 158 allele. Neuropsychopharmacology 34:739–746. https://doi.org/10.1038/npp.2008.132
doi: 10.1038/npp.2008.132
pubmed: 18769474