KEGG   DISEASE: Primary microcephaly
Entry
H00269                      Disease                                
Name
Primary microcephaly
Description
Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by reduced skull circumference and brain volume.
Category
Congenital malformation
Brite
Human diseases [BR:br08402]
 Congenital malformations
  Congenital malformations of the nervous system
   H00269  Primary microcephaly
Human diseases in ICD-11 classification [BR:br08403]
 20 Developmental anomalies
  Structural developmental anomalies primarily affecting one body system
   Structural developmental anomalies of the nervous system
    LA05  Cerebral structural developmental anomalies
     H00269  Primary microcephaly
Network
nt06512  Chromosome cohesion and segregation
nt06515  Regulation of kinetochore-microtubule interactions
Gene
(MCPH1) MCPH1 [HSA:79648] [KO:K19403]
(MCPH2) WDR62 [HSA:284403] [KO:K21762]
(MCPH3) CDK5RAP2 [HSA:55755] [KO:K16542]
(MCPH4) KNL1 [HSA:57082] [KO:K11542]
(MCPH5) ASPM [HSA:259266] [KO:K16743]
(MCPH6) CENPJ [HSA:55835] [KO:K11502]
(MCPH7) STIL [HSA:6491] [KO:K16724]
(MCPH8) CEP135 [HSA:9662] [KO:K16461]
(MCPH9) CEP152 [HSA:22995] [KO:K16728]
(MCPH10) ZNF335 [HSA:63925] [KO:K24371]
(MCPH11) PHC1 [HSA:1911] [KO:K11456]
(MCPH12) CDK6 [HSA:1021] [KO:K02091]
(MCPH13) CENPE [HSA:1062] [KO:K11498]
(MCPH14) SASS6 [HSA:163786] [KO:K16487]
(MCPH15) MFSD2A [HSA:84879] [KO:K23894]
(MCPH16) ANKLE2 [HSA:23141] [KO:K21412]
(MCPH17) CIT [HSA:11113] [KO:K16308]
(MCPH18) WDFY3 [HSA:23001] [KO:K22262]
(MCPH19) COPB2 [HSA:9276] [KO:K17302]
(MCPH20) KIF14 [HSA:9928] [KO:K17915]
(MCPH21) NCAPD2 [HSA:9918] [KO:K06677]
(MCPH22) NCAPD3 [HSA:23310] [KO:K11491]
(MCPH23) NCAPH [HSA:23397] [KO:K06676]
(MCPH24) NUP37 [HSA:79023] [KO:K14302]
(MCPH25) TRAPPC14 [HSA:55262] [KO:K24261]
(MCPH26) LMNB1 [HSA:4001] [KO:K07611]
(MCPH27) LMNB2 [HSA:84823] [KO:K07611]
(MCPH28) RRP7A [HSA:27341] [KO:K14545]
(MCPH29) PDCD6IP [HSA:10015] [KO:K12200]
(MCPH30) BUB1 [HSA:699] [KO:K02178]
Other DBs
ICD-11: LA05.0
ICD-10: Q02
MeSH: D008831
OMIM: 607117 604317 604804 604321 608716 608393 612703 614673 614852 615095 615414 616080 616051 616402 616486 616681 617090 617520 251230 617800 617914 617983 617984 617985 618179 618351 619179 619180 619453 620047 620183
Reference
  Authors
Abuelo D
  Title
Microcephaly syndromes.
  Journal
Semin Pediatr Neurol 14:118-27 (2007)
DOI:10.1016/j.spen.2007.07.003
Reference
  Authors
Cox J, Jackson AP, Bond J, Woods CG
  Title
What primary microcephaly can tell us about brain growth.
  Journal
Trends Mol Med 12:358-66 (2006)
DOI:10.1016/j.molmed.2006.06.006
Reference
  Authors
Woods CG, Bond J, Enard W
  Title
Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings.
  Journal
Am J Hum Genet 76:717-28 (2005)
DOI:10.1086/429930
Reference
PMID:12046007 (MCPH1)
  Authors
Jackson AP, Eastwood H, Bell SM, Adu J, Toomes C, Carr IM, Roberts E, Hampshire DJ, Crow YJ, Mighell AJ, Karbani G, Jafri H, Rashid Y, Mueller RF, Markham AF, Woods CG
  Title
Identification of microcephalin, a protein implicated in determining the size of the human brain.
  Journal
Am J Hum Genet 71:136-42 (2002)
DOI:10.1086/341283
Reference
PMID:21496009 (MCPH2)
  Authors
Bhat V, Girimaji SC, Mohan G, Arvinda HR, Singhmar P, Duvvari MR, Kumar A
  Title
Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations.
  Journal
Clin Genet 80:532-40 (2011)
DOI:10.1111/j.1399-0004.2011.01686.x
Reference
PMID:15793586 (MCPH3 MCPH6)
  Authors
Bond J, Roberts E, Springell K, Lizarraga SB, Scott S, Higgins J, Hampshire DJ, Morrison EE, Leal GF, Silva EO, Costa SM, Baralle D, Raponi M, Karbani G, Rashid Y, Jafri H, Bennett C, Corry P, Walsh CA, Woods CG
  Title
A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size.
  Journal
Nat Genet 37:353-5 (2005)
DOI:10.1038/ng1539
Reference
PMID:22983954 (MCPH4)
  Authors
Genin A, Desir J, Lambert N, Biervliet M, Van Der Aa N, Pierquin G, Killian A, Tosi M, Urbina M, Lefort A, Libert F, Pirson I, Abramowicz M
  Title
Kinetochore KMN network gene CASC5 mutated in primary microcephaly.
  Journal
Hum Mol Genet 21:5306-17 (2012)
DOI:10.1093/hmg/dds386
Reference
PMID:12355089 (MCPH5)
  Authors
Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K, Mahadevan M, Crow YJ, Markham AF, Walsh CA, Woods CG
  Title
ASPM is a major determinant of cerebral cortical size.
  Journal
Nat Genet 32:316-20 (2002)
DOI:10.1038/ng995
Reference
PMID:19215732 (MCPH7)
  Authors
Kumar A, Girimaji SC, Duvvari MR, Blanton SH
  Title
Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly.
  Journal
Am J Hum Genet 84:286-90 (2009)
DOI:10.1016/j.ajhg.2009.01.017
Reference
PMID:22521416 (MCPH8)
  Authors
Hussain MS, Baig SM, Neumann S, Nurnberg G, Farooq M, Ahmad I, Alef T, Hennies HC, Technau M, Altmuller J, Frommolt P, Thiele H, Noegel AA, Nurnberg P
  Title
A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function.
  Journal
Am J Hum Genet 90:871-8 (2012)
DOI:10.1016/j.ajhg.2012.03.016
Reference
PMID:20598275 (MCPH9)
  Authors
Guernsey DL, Jiang H, Hussin J, Arnold M, Bouyakdan K, Perry S, Babineau-Sturk T, Beis J, Dumas N, Evans SC, Ferguson M, Matsuoka M, Macgillivray C, Nightingale M, Patry L, Rideout AL, Thomas A, Orr A, Hoffmann I, Michaud JL, Awadalla P, Meek DC, Ludman M, Samuels ME
  Title
Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4.
  Journal
Am J Hum Genet 87:40-51 (2010)
DOI:10.1016/j.ajhg.2010.06.003
Reference
PMID:23178126 (MCPH10)
  Authors
Yang YJ, Baltus AE, Mathew RS, Murphy EA, Evrony GD, Gonzalez DM, Wang EP, Marshall-Walker CA, Barry BJ, Murn J, Tatarakis A, Mahajan MA, Samuels HH, Shi Y, Golden JA, Mahajnah M, Shenhav R, Walsh CA
  Title
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.
  Journal
Cell 151:1097-112 (2012)
DOI:10.1016/j.cell.2012.10.043
Reference
PMID:23418308 (MCPH11)
  Authors
Awad S, Al-Dosari MS, Al-Yacoub N, Colak D, Salih MA, Alkuraya FS, Poizat C
  Title
Mutation in PHC1 implicates chromatin remodeling in primary microcephaly pathogenesis.
  Journal
Hum Mol Genet 22:2200-13 (2013)
DOI:10.1093/hmg/ddt072
Reference
PMID:23918663 (MCPH12)
  Authors
Hussain MS, Baig SM, Neumann S, Peche VS, Szczepanski S, Nurnberg G, Tariq M, Jameel M, Khan TN, Fatima A, Malik NA, Ahmad I, Altmuller J, Frommolt P, Thiele H, Hohne W, Yigit G, Wollnik B, Neubauer BA, Nurnberg P, Noegel AA
  Title
CDK6 associates with the centrosome during mitosis and is mutated in a large Pakistani family with primary microcephaly.
  Journal
Hum Mol Genet 22:5199-214 (2013)
DOI:10.1093/hmg/ddt374
Reference
PMID:24748105 (MCPH13)
  Authors
Mirzaa GM, Vitre B, Carpenter G, Abramowicz I, Gleeson JG, Paciorkowski AR, Cleveland DW, Dobyns WB, O'Driscoll M
  Title
Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism.
  Journal
Hum Genet 133:1023-39 (2014)
DOI:10.1007/s00439-014-1443-3
Reference
PMID:24951542 (MCPH14)
  Authors
Khan MA, Rupp VM, Orpinell M, Hussain MS, Altmuller J, Steinmetz MO, Enzinger C, Thiele H, Hohne W, Nurnberg G, Baig SM, Ansar M, Nurnberg P, Vincent JB, Speicher MR, Gonczy P, Windpassinger C
  Title
A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.
  Journal
Hum Mol Genet 23:5940-9 (2014)
DOI:10.1093/hmg/ddu318
Reference
PMID:26005865 (MCPH15)
  Authors
Alakbarzade V, Hameed A, Quek DQ, Chioza BA, Baple EL, Cazenave-Gassiot A, Nguyen LN, Wenk MR, Ahmad AQ, Sreekantan-Nair A, Weedon MN, Rich P, Patton MA, Warner TT, Silver DL, Crosby AH
  Title
A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome.
  Journal
Nat Genet 47:814-7 (2015)
DOI:10.1038/ng.3313
Reference
PMID:25259927 (MCPH16)
  Authors
Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, Wiszniewski W, Sandoval H, Haelterman NA, Xiong B, Zhang K, Bayat V, David G, Li T, Chen K, Gala U, Harel T, Pehlivan D, Penney S, Vissers LE, de Ligt J, Jhangiani SN, Xie Y, Tsang SH, Parman Y, Sivaci M, Battaloglu E, Muzny D, Wan YW, Liu Z, Lin-Moore AT, Clark RD, Curry CJ, Link N, Schulze KL, Boerwinkle E, Dobyns WB, Allikmets R, Gibbs RA, Chen R, Lupski JR, Wangler MF, Bellen HJ
  Title
A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases.
  Journal
Cell 159:200-14 (2014)
DOI:10.1016/j.cell.2014.09.002
Reference
PMID:27519304 (MCPH17)
  Authors
Basit S, Al-Harbi KM, Alhijji SA, Albalawi AM, Alharby E, Eldardear A, Samman MI
  Title
CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly.
  Journal
Hum Genet 135:1199-207 (2016)
DOI:10.1007/s00439-016-1724-0
Reference
PMID:27008544 (MCPH18)
  Authors
Kadir R, Harel T, Markus B, Perez Y, Bakhrat A, Cohen I, Volodarsky M, Feintsein-Linial M, Chervinski E, Zlotogora J, Sivan S, Birnbaum RY, Abdu U, Shalev S, Birk OS
  Title
ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.
  Journal
PLoS Genet 12:e1005919 (2016)
DOI:10.1371/journal.pgen.1005919
Reference
PMID:29036432 (MCPH19)
  Authors
DiStasio A, Driver A, Sund K, Donlin M, Muraleedharan RM, Pooya S, Kline-Fath B, Kaufman KM, Prows CA, Schorry E, Dasgupta B, Stottmann RW
  Title
Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly.
  Journal
Hum Mol Genet 26:4836-4848 (2017)
DOI:10.1093/hmg/ddx362
Reference
PMID:28892560 (MCPH20)
  Authors
Moawia A, Shaheen R, Rasool S, Waseem SS, Ewida N, Budde B, Kawalia A, Motameny S, Khan K, Fatima A, Jameel M, Ullah F, Akram T, Ali Z, Abdullah U, Irshad S, Hohne W, Noegel AA, Al-Owain M, Hortnagel K, Stobe P, Baig SM, Nurnberg P, Alkuraya FS, Hahn A, Hussain MS
  Title
Mutations of KIF14 cause primary microcephaly by impairing cytokinesis.
  Journal
Ann Neurol 82:562-577 (2017)
DOI:10.1002/ana.25044
Reference
PMID:27737959 (MCPH21 MCPH22 MCPH23)
  Authors
Martin CA, Murray JE, Carroll P, Leitch A, Mackenzie KJ, Halachev M, Fetit AE, Keith C, Bicknell LS, Fluteau A, Gautier P, Hall EA, Joss S, Soares G, Silva J, Bober MB, Duker A, Wise CA, Quigley AJ, Phadke SR, Wood AJ, Vagnarelli P, Jackson AP
  Title
Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis.
  Journal
Genes Dev 30:2158-2172 (2016)
DOI:10.1101/gad.286351.116
Reference
PMID:30179222 (MCPH24)
  Authors
Braun DA, Lovric S, Schapiro D, Schneider R, Marquez J, Asif M, Hussain MS, Daga A, Widmeier E, Rao J, Ashraf S, Tan W, Lusk CP, Kolb A, Jobst-Schwan T, Schmidt JM, Hoogstraten CA, Eddy K, Kitzler TM, Shril S, Moawia A, Schrage K, Khayyat AIA, Lawson JA, Gee HY, Warejko JK, Hermle T, Majmundar AJ, Hugo H, Budde B, Motameny S, Altmuller J, Noegel AA, Fathy HM, Gale DP, Waseem SS, Khan A, Kerecuk L, Hashmi S, Mohebbi N, Ettenger R, Serdaroglu E, Alhasan KA, Hashem M, Goncalves S, Ariceta G, Ubetagoyena M, Antonin W, Baig SM, Alkuraya FS, Shen Q, Xu H, Antignac C, Lifton RP, Mane S, Nurnberg P, Khokha MK, Hildebrandt F
  Title
Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome.
  Journal
J Clin Invest 128:4313-4328 (2018)
DOI:10.1172/JCI98688
Reference
PMID:30715179 (MCPH25)
  Authors
Perez Y, Bar-Yaacov R, Kadir R, Wormser O, Shelef I, Birk OS, Flusser H, Birnbaum RY
  Title
Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish.
  Journal
Brain 142:574-585 (2019)
DOI:10.1093/brain/awz004
Reference
PMID:32910914 (MCPH26)
  Authors
Cristofoli F, Moss T, Moore HW, Devriendt K, Flanagan-Steet H, May M, Jones J, Roelens F, Fons C, Fernandez A, Martorell L, Selicorni A, Maitz S, Vitiello G, Van der Hoeven G, Skinner SA, Bollen M, Vermeesch JR, Steet R, Van Esch H
  Title
De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity.
  Journal
Am J Hum Genet 107:753-762 (2020)
DOI:10.1016/j.ajhg.2020.08.015
Reference
PMID:33033404 (MCPH27)
  Authors
Parry DA, Martin CA, Greene P, Marsh JA, Blyth M, Cox H, Donnelly D, Greenhalgh L, Greville-Heygate S, Harrison V, Lachlan K, McKenna C, Quigley AJ, Rea G, Robertson L, Suri M, Jackson AP
  Title
Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.
  Journal
Genet Med 23:408-414 (2021)
DOI:10.1038/s41436-020-00980-3
Reference
PMID:33199730 (MCPH28)
  Authors
Farooq M, Lindbaek L, Krogh N, Doganli C, Keller C, Monnich M, Goncalves AB, Sakthivel S, Mang Y, Fatima A, Andersen VS, Hussain MS, Eiberg H, Hansen L, Kjaer KW, Gopalakrishnan J, Pedersen LB, Mollgard K, Nielsen H, Baig SM, Tommerup N, Christensen ST, Larsen LA
  Title
RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis.
  Journal
Nat Commun 11:5816 (2020)
DOI:10.1038/s41467-020-19658-0
Reference
PMID:32286682 (MCPH29)
  Authors
Khan A, Alaamery M, Massadeh S, Obaid A, Kashgari AA, Walsh CA, Eyaid W
  Title
PDCD6IP, encoding a regulator of the ESCRT complex, is mutated in microcephaly.
  Journal
Clin Genet 98:80-85 (2020)
DOI:10.1111/cge.13756
Reference
PMID:35044816 (MCPH30)
  Authors
Carvalhal S, Bader I, Rooimans MA, Oostra AB, Balk JA, Feichtinger RG, Beichler C, Speicher MR, van Hagen JM, Waisfisz Q, van Haelst M, Bruijn M, Tavares A, Mayr JA, Wolthuis RMF, Oliveira RA, de Lange J
  Title
Biallelic BUB1 mutations cause microcephaly, developmental delay, and variable effects on cohesion and chromosome segregation.
  Journal
Sci Adv 8:eabk0114 (2022)
DOI:10.1126/sciadv.abk0114

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