MCID: PRM212
MIFTS: 41

Primary Microcephaly

Categories: Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Primary Microcephaly

MalaCards integrated aliases for Primary Microcephaly:

Name: Primary Microcephaly 12 36 29 6 15
Microcephaly, Primary 54
True Microcephaly 12

Classifications:



External Ids:

Disease Ontology 12 DOID:0070297
KEGG 36 H00269

Summaries for Primary Microcephaly

Disease Ontology : 12 A microcephaly characterized by microcephaly present at birth, where the brain is small but has normal architecture, and nonprogressive mental retardation.

MalaCards based summary : Primary Microcephaly, also known as microcephaly, primary, is related to microcephaly 1, primary, autosomal recessive and microcephaly 9, primary, autosomal recessive. An important gene associated with Primary Microcephaly is PHC1 (Polyhomeotic Homolog 1), and among its related pathways/superpathways are Cell Cycle, Mitotic and Organelle biogenesis and maintenance. Affiliated tissues include brain, eye and bone, and related phenotypes are Effect on mitosis and growth/size/body region

KEGG : 36 Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by reduced skull circumference and brain volume.

Related Diseases for Primary Microcephaly

Diseases in the Microcephaly family:

Microcephaly, Autosomal Dominant Microcephaly 1, Primary, Autosomal Recessive
Microcephaly 4, Primary, Autosomal Recessive Microcephaly 3, Primary, Autosomal Recessive
Microcephaly 6, Primary, Autosomal Recessive Microcephaly 5, Primary, Autosomal Recessive
Microcephaly 7, Primary, Autosomal Recessive Microcephaly 8, Primary, Autosomal Recessive
Microcephaly 9, Primary, Autosomal Recessive Microcephaly 10, Primary, Autosomal Recessive
Microcephaly 11, Primary, Autosomal Recessive Microcephaly 13, Primary, Autosomal Recessive
Microcephaly 12, Primary, Autosomal Recessive Microcephaly 14, Primary, Autosomal Recessive
Microcephaly 15, Primary, Autosomal Recessive Microcephaly 16, Primary, Autosomal Recessive
Microcephaly 17, Primary, Autosomal Recessive Microcephaly 18, Primary, Autosomal Dominant
Microcephaly 19, Primary, Autosomal Recessive Microcephaly 20, Primary, Autosomal Recessive
Microcephaly 21, Primary, Autosomal Recessive Microcephaly 22, Primary, Autosomal Recessive
Microcephaly 23, Primary, Autosomal Recessive Microcephaly 24, Primary, Autosomal Recessive
Microcephaly 25, Primary, Autosomal Recessive Primary Autosomal Recessive Microcephaly
Primary Microcephaly

Diseases related to Primary Microcephaly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 114)
# Related Disease Score Top Affiliating Genes
1 microcephaly 1, primary, autosomal recessive 33.7 MCPH1 CEP152 CENPJ ASPM
2 microcephaly 9, primary, autosomal recessive 32.8 WDR62 STIL KNL1 CEP152 CEP135 CENPJ
3 microcephaly 18, primary, autosomal dominant 32.7 CEP152 CEP135 CENPJ
4 microcephaly 4, primary, autosomal recessive 32.6 WDR62 STIL MCPH1 KNL1 CEP152 CEP135
5 galloway-mowat syndrome 32.4 WDR62 TPRKB TP53RK
6 microcephaly 8, primary, autosomal recessive 32.4 WDR62 STIL MCPH1 KNL1 CEP152 CEP135
7 microcephaly 5, primary, autosomal recessive 32.4 WDR62 STIL PHC1 MCPH1 KNL1 CEP152
8 microcephaly 6, primary, autosomal recessive 32.3 WDR62 STIL MCPH1 CEP152 CEP135 CENPJ
9 primary autosomal recessive microcephaly 32.3 WDR62 STIL SASS6 RTTN PHC1 MCPH1
10 microcephaly 17, primary, autosomal recessive 32.2 WDR62 STIL MCPH1 CIT CEP152 CENPJ
11 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 32.2 WDR62 STIL PHC1 MCPH1 KNL1 CEP152
12 microcephaly 7, primary, autosomal recessive 32.2 WDR62 STIL MCPH1 KNL1 CEP152 CEP135
13 microcephaly 10, primary, autosomal recessive 32.1 WDR62 PHC1 CEP152 CEP135
14 microcephaly 3, primary, autosomal recessive 32.0 WDR62 STIL MCPH1 KNL1 CEP63 CEP152
15 microcephaly with or without chorioretinopathy, lymphedema, or mental retardation 30.4 RTTN ASPM
16 microcephaly 14, primary, autosomal recessive 30.1 SASS6 RTTN
17 seckel syndrome 6 30.1 CEP63 CEP152
18 microcephaly 12, primary, autosomal recessive 30.0 WDR62 STIL MCPH1 KNL1 CEP152 CEP135
19 microcephaly 11, primary, autosomal recessive 29.9 WDR62 PHC1 MCPH1 CEP152 CEP135 CENPJ
20 meier-gorlin syndrome 1 29.8 WDR62 SASS6 CEP63 CEP152 CEP135 CENPJ
21 periventricular nodular heterotopia 29.8 WDR62 STIL RTTN MCPH1 CENPJ CDK5RAP2
22 microcephalic osteodysplastic primordial dwarfism, type ii 29.8 STIL MCPH1 CEP63 CEP152 CEP135 CENPJ
23 seckel syndrome 1 29.7 CEP152 CENPJ
24 isolated growth hormone deficiency, type ia 29.7 WDR62 STIL SASS6 RTTN MCPH1 CEP63
25 microcephaly 29.4 WDR62 TSEN15 TPRKB TP53RK STIL SASS6
26 seckel syndrome 29.3 WDR62 STIL SASS6 RTTN PNKP PHC1
27 primary microcephaly-mild intellectual disability-young-onset diabetes syndrome 12.3
28 mental retardation, autosomal dominant 7 11.3
29 microcephaly, autosomal dominant 11.3
30 microcephaly, epilepsy, and diabetes syndrome 11.1
31 microcephaly, seizures, and developmental delay 11.0
32 neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies 11.0
33 microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome 11.0
34 autosomal recessive chorioretinopathy-microcephaly syndrome 11.0
35 seckel syndrome 2 10.5 CEP152 CENPJ CDK5RAP2
36 seckel syndrome 4 10.5 MCPH1 CEP152 CENPJ
37 alacrima, achalasia, and mental retardation syndrome 10.4
38 microcephaly 13, primary, autosomal recessive 10.4 WDR62 RTTN
39 seckel syndrome 5 10.4 MCPH1 CEP63 CEP152 CENPJ
40 bladder calculus 10.3 TPRKB TP53RK
41 lower urinary tract calculus 10.3 TPRKB TP53RK
42 joubert syndrome 1 10.3 SASS6 MCPH1 CEP152 CENPJ CDK5RAP2
43 lissencephaly 2 10.3 WDR62 CEP152
44 autosomal recessive non-syndromic intellectual disability 10.3 WDR62 STIL MCPH1 CEP152 CEP135 CDK5RAP2
45 physical disorder 10.1 WDR62 STIL MCPH1 CEP152 CEP135 CENPJ
46 autosomal recessive disease 10.1
47 dwarfism 10.1
48 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.0
49 polymicrogyria 10.0
50 nijmegen breakage syndrome 9.9

Graphical network of the top 20 diseases related to Primary Microcephaly:



Diseases related to Primary Microcephaly

Symptoms & Phenotypes for Primary Microcephaly

GenomeRNAi Phenotypes related to Primary Microcephaly according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Effect on mitosis GR00257-A-2 9.02 ASPM CEP135 CIT MCPH1 SASS6

MGI Mouse Phenotypes related to Primary Microcephaly:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.24 ASPM CDK5RAP2 CDK6 CENPJ CEP135 CEP63
2 cellular MP:0005384 10.22 ASPM CDK5RAP2 CDK6 CENPJ CEP152 CEP63
3 hematopoietic system MP:0005397 10.02 ASPM CDK5RAP2 CDK6 CENPJ DYRK1A KNL1
4 immune system MP:0005387 9.96 ASPM CDK5RAP2 CDK6 CENPJ DYRK1A KNL1
5 mortality/aging MP:0010768 9.93 CDK5RAP2 CDK6 CENPJ CEP135 CIT DYRK1A
6 nervous system MP:0003631 9.8 ASPM CDK5RAP2 CDK6 CENPJ CEP152 CEP63
7 reproductive system MP:0005389 9.28 ASPM CDK5RAP2 CDK6 CENPJ CEP63 CIT

Drugs & Therapeutics for Primary Microcephaly

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Microcephaly Genetic Deficiency in Neural Progenitors: Genotyping, Phenotyping and Functional Neuro-anatomy and Neurobiology Comparative Primitive Microcephaly (MCPH) and the Fanconi Anemia (FA) Completed NCT01565005

Search NIH Clinical Center for Primary Microcephaly

Genetic Tests for Primary Microcephaly

Genetic tests related to Primary Microcephaly:

# Genetic test Affiliating Genes
1 Primary Microcephaly 29

Anatomical Context for Primary Microcephaly

MalaCards organs/tissues related to Primary Microcephaly:

40
Brain, Eye, Bone, Cortex, Bone Marrow, Lung, Kidney

Publications for Primary Microcephaly

Articles related to Primary Microcephaly:

(show top 50) (show all 365)
# Title Authors PMID Year
1
Mutation analysis of the ASPM gene in 18 Pakistani families with autosomal recessive primary microcephaly. 54 61
19808985 2010
2
BRIT1/MCPH1 is essential for mitotic and meiotic recombination DNA repair and maintaining genomic stability in mice. 54 61
20107607 2010
3
Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations. 54 61
19770472 2009
4
Compound heterozygous ASPM mutations associated with microcephaly and simplified cortical gyration in a consanguineous Algerian family. 54 61
19332161 2009
5
Microcephalin regulates BRCA2 and Rad51-associated DNA double-strand break repair. 54 61
19549900 2009
6
Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1. 54 61
19546241 2009
7
The c.940G variant of the Microcephalin (MCPH1) gene is not associated with microcephaly or mental retardation. 54 61
19267414 2009
8
Expression analysis of the autosomal recessive primary microcephaly genes MCPH1 (microcephalin) and MCPH5 (ASPM, abnormal spindle-like, microcephaly associated) in human malignant gliomas. 54 61
18636190 2008
9
MCPH1 functions in an H2AX-dependent but MDC1-independent pathway in response to DNA damage. 54 61
17925396 2007
10
The Drosophila homolog of MCPH1, a human microcephaly gene, is required for genomic stability in the early embryo. 54 61
17895362 2007
11
Microcephalin coordinates mitosis in the syncytial Drosophila embryo. 54 61
17895363 2007
12
Previously described sequence variant in CDK5RAP2 gene in a Pakistani family with autosomal recessive primary microcephaly. 54 61
17764569 2007
13
Novel protein-truncating mutations in the ASPM gene in families with autosomal recessive primary microcephaly. 54 61
17849285 2007
14
The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. 54 61
17220170 2007
15
What primary microcephaly can tell us about brain growth. 54 61
16829198 2006
16
Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ. 54 61
16631324 2006
17
A novel domain suggests a ciliary function for ASPM, a brain size determining gene. 54 61
16443634 2006
18
Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: Novel sequence variants in ASPM gene. 54 61
16673149 2006
19
Misregulated chromosome condensation in MCPH1 primary microcephaly is mediated by condensin II. 54 61
16434882 2006
20
A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly. 54 61
16900296 2006
21
BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly. 54 61
16217032 2005
22
ASPM mutations identified in patients with primary microcephaly and seizures. 54 61
16141009 2005
23
Evolution of primary microcephaly genes and the enlargement of primate brains. 54 61
15917198 2005
24
Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations. 54 61
15355437 2004
25
Mutations in microcephalin cause aberrant regulation of chromosome condensation. 54 61
15199523 2004
26
Microcephalin is a DNA damage response protein involved in regulation of CHK1 and BRCA1. 54 61
15220350 2004
27
A translocation breakpoint disrupts the ASPM gene in a patient with primary microcephaly. 54 61
14997185 2004
28
Human microcephaly. 54 61
15018946 2004
29
Protein-truncating mutations in ASPM cause variable reduction in brain size. 54 61
14574646 2003
30
Primary microcephaly: microcephalin and ASPM determine the size of the human brain. 54 61
12571366 2002
31
Just Expect It: Compound Heterozygous Variants of POMT1 in a Consanguineous Family-The Role of Next Generation Sequencing in Neuromuscular Disorders. 61
31627234 2020
32
CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects. 61
32015000 2020
33
Congenital microcephaly-linked CDK5RAP2 affects eye development. 61
31355417 2020
34
Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins. 61
31936331 2020
35
High-mobility group nucleosomal binding domain 2 protects against microcephaly by maintaining global chromatin accessibility during corticogenesis. 61
31699896 2020
36
Genetic study of Khyber-Pukhtunkhwa resident Pakistani families presenting primary microcephaly with intellectual disability. 61
31853109 2019
37
Rare missense TUBGCP5 gene variant in a patient with primary microcephaly. 61
30543990 2019
38
Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways. 61
31696992 2019
39
A Novel Frameshift Mutation in Abnormal Spindle-Like Microcephaly (ASPM) Gene in an Iranian Patient with Primary Microcephaly: A Case Report. 61
31970108 2019
40
[Update on autosomal recessive primary microcephaly (MCPH)-associated proteins]. 61
31624053 2019
41
Evolution of ASPM coding variation in apes and associations with brain structure in chimpanzees. 61
31119860 2019
42
Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly. 61
30842647 2019
43
Altered inhibition and excitation in neocortical circuits in congenital microcephaly. 61
31102767 2019
44
Cilia in hereditary cerebral anomalies. 61
31177551 2019
45
10q23.31 microduplication encompassing PTEN decreases mTOR signalling activity and is associated with autosomal dominant primary microcephaly. 61
30301738 2019
46
A novel homozygous splice-site variant of NCAPD2 gene identified in two siblings with primary microcephaly: The second case report. 61
31056748 2019
47
Primary microcephaly, primordial dwarfism, and brachydactyly in adult cases with biallelic skipping of RTTN exon 42. 61
30927481 2019
48
MCPH1 is essential for cellular adaptation to the G2-phase decatenation checkpoint. 61
30964711 2019
49
Modeling microcephaly with cerebral organoids reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly in neural progenitors. 61
31197141 2019
50
A novel WDR62 missense mutation in microcephaly with abnormal cortical architecture and review of the literature. 61
30706430 2019

Variations for Primary Microcephaly

ClinVar genetic disease variations for Primary Microcephaly:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TSEN15 NM_052965.4(TSEN15):c.226T>G (p.Trp76Gly)SNV Pathogenic/Likely pathogenic 183315 rs730882223 1:184023870-184023870 1:184054736-184054736
2 PHC1 NM_004426.3(PHC1):c.2974C>T (p.Leu992Phe)SNV Pathogenic/Likely pathogenic 65406 rs587777036 12:9092014-9092014 12:8939418-8939418
3 TUBA3E NM_207312.3(TUBA3E):c.643C>T (p.Arg215Cys)SNV Likely pathogenic 183299 rs730882212 2:130951772-130951772 2:130194199-130194199
4 OCLN NM_001205254.2(OCLN):c.514dup (p.Tyr172fs)duplication Likely pathogenic 183322 rs730882227 5:68805430-68805431 5:69509603-69509604
5 INO80 NM_017553.3(INO80):c.3737G>A (p.Arg1246Gln)SNV Likely pathogenic 183320 rs199722402 15:41279384-41279384 15:40987186-40987186
6 INO80 NM_017553.3(INO80):c.1501T>C (p.Ser501Pro)SNV Likely pathogenic 183321 rs730882226 15:41364151-41364151 15:41071953-41071953
7 PNKP NM_007254.4(PNKP):c.1251_1252insACGGGTCGCCATCGACA (p.Arg418fs)insertion Likely pathogenic 183318 rs730882224 19:50365075-50365076 19:49861818-49861819
8 MCPH1 NM_024596.3(MCPH1):c.1_114deldeletion Likely pathogenic 183323

Expression for Primary Microcephaly

Search GEO for disease gene expression data for Primary Microcephaly.

Pathways for Primary Microcephaly

Pathways related to Primary Microcephaly according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.44 MCPH1 KNL1 DYRK1A CEP63 CEP152 CEP135
2
Show member pathways
12.08 CEP63 CEP152 CEP135 CENPJ CDK5RAP2

GO Terms for Primary Microcephaly

Cellular components related to Primary Microcephaly according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.22 WDR62 TPRKB TP53RK STIL SASS6 RTTN
2 cytosol GO:0005829 10.21 WDR62 TPRKB STIL SASS6 KNL1 CIT
3 nucleoplasm GO:0005654 10.19 TSEN15 TP53RK PNKP PHC1 MCPH1 KNL1
4 microtubule organizing center GO:0005815 9.91 WDR62 SASS6 RTTN MCPH1 CEP63 CEP152
5 cytoskeleton GO:0005856 9.8 WDR62 STIL SASS6 RTTN MCPH1 DYRK1A
6 centriole GO:0005814 9.76 WDR62 STIL SASS6 RTTN CEP63 CEP152
7 spindle pole GO:0000922 9.65 WDR62 CEP63 CDK5RAP2
8 mitotic spindle pole GO:0097431 9.51 CDK5RAP2 ASPM
9 pericentriolar material GO:0000242 9.46 CEP152 CDK5RAP2
10 EKC/KEOPS complex GO:0000408 9.4 TPRKB TP53RK
11 deuterosome GO:0098536 9.37 SASS6 CEP152
12 centrosome GO:0005813 9.36 WDR62 STIL SASS6 RTTN CEP63 CEP152

Biological processes related to Primary Microcephaly according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 9.97 TP53RK PNKP DYRK1A CIT CDK6
2 cell cycle GO:0007049 9.91 SASS6 KNL1 CIT CEP63 CDK6 ASPM
3 cell division GO:0051301 9.85 KNL1 CIT CEP63 CENPJ CDK6 ASPM
4 tRNA processing GO:0008033 9.72 TSEN15 TPRKB TP53RK
5 ciliary basal body-plasma membrane docking GO:0097711 9.72 CEP63 CEP152 CEP135 CENPJ CDK5RAP2
6 cerebral cortex development GO:0021987 9.69 WDR62 MCPH1 ASPM
7 regulation of G2/M transition of mitotic cell cycle GO:0010389 9.65 CEP63 CEP152 CEP135 CENPJ CDK5RAP2
8 G2/M transition of mitotic cell cycle GO:0000086 9.63 CIT CEP63 CEP152 CEP135 CENPJ CDK5RAP2
9 neuronal stem cell population maintenance GO:0097150 9.57 MCPH1 ASPM
10 protein localization to centrosome GO:0071539 9.56 STIL MCPH1
11 generation of neurons GO:0048699 9.54 CIT CDK6
12 centriole-centriole cohesion GO:0010457 9.52 RTTN CEP135
13 regulation of centriole replication GO:0046599 9.49 STIL CENPJ
14 positive regulation of non-motile cilium assembly GO:1902857 9.48 CEP135 CENPJ
15 positive regulation of establishment of protein localization GO:1904951 9.46 CEP135 CENPJ
16 de novo centriole assembly involved in multi-ciliated epithelial cell differentiation GO:0098535 9.4 CEP63 CEP152
17 centrosome duplication GO:0051298 9.26 STIL SASS6 CEP152 CENPJ
18 centriole replication GO:0007099 9.23 WDR62 SASS6 RTTN CEP63 CEP152 CEP135

Molecular functions related to Primary Microcephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.58 WDR62 TPRKB TP53RK STIL SASS6 PNKP
2 kinase activity GO:0016301 9.35 TP53RK PNKP DYRK1A CIT CDK6

Sources for Primary Microcephaly

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....