KEGG DISEASE: Primary microcephaly

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 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
Pathway-based classification of diseases [BR:br08402]
Cellular process
  nt06523  Epigenetic regulation by Polycomb complexes
   H00269  Primary microcephaly
  nt06512  Chromosome cohesion and segregation
   H00269  Primary microcephaly
  nt06515  Regulation of kinetochore-microtubule interactions
   H00269  Primary microcephaly
  nt06539  Cytoskeleton in muscle cells
   H00269  Primary microcephaly
  nt06541  Cytoskeleton in neurons
   H00269  Primary microcephaly

Pathway

hsa04820

Cytoskeleton in muscle cells

hsa04110

Cell cycle

Network

nt06512 Chromosome cohesion and segregation
nt06515 Regulation of kinetochore-microtubule interactions
nt06523 Epigenetic regulation by Polycomb complexes
nt06539 Cytoskeleton in muscle cells
nt06541 Cytoskeleton in neurons

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

Reference

PMID:17980308

Authors

Abuelo D

Title

Microcephaly syndromes.

Journal

Semin Pediatr Neurol 14:118-27 (2007)
DOI:10.1016/j.spen.2007.07.003

Reference

PMID:16829198

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

PMID:15806441

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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