Details of Disease

General Information of Disease (ID: DIS29IE3)

• Disease Name: Autosomal recessive primary microcephaly
• Synonyms: true microcephaly; microcephaly, primary autosomal recessive; microcephaly, primary, autosomal recessive; microcephalia vera; MCPH; microcephaly vera
• Definition: Autosomal recessive primary microcephaly (MCPH) is a rare genetically heterogeneous disorder of neurogenic brain development characterized by reduced head circumference at birth with no gross anomalies of brain architecture and variable degrees of intellectual impairment.
• Disease Hierarchy:
  DISUXHZ6: Isolated congenital microcephaly
  DISCPWH9: Autosomal recessive disease
  DISYOKTG: Mendelian neurodevelopmental disorder
  DIS29IE3: Autosomal recessive primary microcephaly
• Disease Identifiers:
  MONDO ID: MONDO_0016660
  MESH ID: C579935
  UMLS CUI: C3711387
  MedGen ID: 777995
  Orphanet ID: 2512
  SNOMED CT ID: 715981004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 27 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
WDR62	OTJ85ZXF	Supportive	Autosomal recessive	[1]
CENPE	OTQ7AP04	Limited	Autosomal recessive	[2]
ANKLE2	OTHCYR6Y	Supportive	Autosomal recessive	[7]
CDK6	OTR95N0X	Supportive	Autosomal recessive	[3]
CENPJ	OTZCQZN5	Supportive	Autosomal recessive	[1]
CEP135	OT1O9XYJ	Supportive	Autosomal recessive	[1]
CEP152	OTOKZR9B	Supportive	Autosomal recessive	[1]
CEP63	OTX3TTZH	Supportive	Autosomal recessive	[1]
CIT	OTOZDKPG	Supportive	Autosomal recessive	[4]
COPB2	OT82JIGC	Supportive	Autosomal recessive	[8]
KNL1	OT4Q3LHV	Supportive	Autosomal recessive	[1]
MCPH1	OTYT3TT5	Supportive	Autosomal recessive	[1]
METTL5	OTR0OO41	Supportive	Autosomal recessive	[9]
MFSD2A	OTVG1VG0	Supportive	Autosomal recessive	[6]
NCAPD3	OTOZY2UL	Supportive	Autosomal recessive	[10]
PHC1	OT1JMX8U	Supportive	Autosomal recessive	[1]
PYCR2	OTS2HLGD	Supportive	Autosomal recessive	[11]
SASS6	OT1V8H40	Supportive	Autosomal recessive	[12]
TAF13	OT1XMYAD	Supportive	Autosomal recessive	[13]
TRAPPC14	OTN9TK2O	Supportive	Autosomal recessive	[14]
ASPM	OTKXQMNA	Strong	Autosomal recessive	[2]
OXA1L	OTS0BFRD	Strong	Genetic Variation	[3]
PCNT	OTW4Z65J	Strong	Biomarker	[15]
SDR42E1	OTTTLPRH	Strong	Biomarker	[16]
CDK5RAP2	OTRKEVTY	Definitive	Autosomal recessive	[2]
KIF14	OTXHT4JM	Definitive	Autosomal recessive	[17]
STIL	OT9799VN	Definitive	Autosomal recessive	[2]

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CENPE	TTZD5QR	Limited	Autosomal recessive	[2]
CDK6	TTO0FDJ	Supportive	Autosomal recessive	[3]
CIT	TT3BKTU	Supportive	Autosomal recessive	[4]
CDK6	TTO0FDJ	Strong	Genetic Variation	[5]
CIT	TT3BKTU	Strong	GermlineCausalMutation	[4]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
MFSD2A	DT5G94L	Supportive	Autosomal recessive	[6]

References

• [1] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] CDK6 associates with the centrosome during mitosis and is mutated in a large Pakistani family with primary microcephaly. Hum Mol Genet. 2013 Dec 20;22(25):5199-214. doi: 10.1093/hmg/ddt374. Epub 2013 Aug 4.
• [4] Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly. Am J Hum Genet. 2016 Aug 4;99(2):501-10. doi: 10.1016/j.ajhg.2016.07.004. Epub 2016 Jul 21.
• [5] Molecular genetics of human primary microcephaly: an overview.BMC Med Genomics. 2015;8 Suppl 1(Suppl 1):S4. doi: 10.1186/1755-8794-8-S1-S4. Epub 2015 Jan 15.
• [6] A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome. Nat Genet. 2015 Jul;47(7):814-7. doi: 10.1038/ng.3313. Epub 2015 May 25.
• [7] A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell. 2014 Sep 25;159(1):200-214. doi: 10.1016/j.cell.2014.09.002.
• [8] Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly. Hum Mol Genet. 2017 Dec 15;26(24):4836-4848. doi: 10.1093/hmg/ddx362.
• [9] Bi-allelic Variants in METTL5 Cause Autosomal-Recessive Intellectual Disability and Microcephaly. Am J Hum Genet. 2019 Oct 3;105(4):869-878. doi: 10.1016/j.ajhg.2019.09.007. Epub 2019 Sep 26.
• [10] Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis. Genes Dev. 2016 Oct 1;30(19):2158-2172. doi: 10.1101/gad.286351.116. Epub 2016 Oct 13.
• [11] Homozygous variants in pyrroline-5-carboxylate reductase 2 (PYCR2) in patients with progressive microcephaly and hypomyelinating leukodystrophy. Am J Med Genet A. 2017 Feb;173(2):460-470. doi: 10.1002/ajmg.a.38049. Epub 2016 Nov 11.
• [12] A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family. Hum Mol Genet. 2014 Nov 15;23(22):5940-9. doi: 10.1093/hmg/ddu318. Epub 2014 Jun 20.
• [13] Hypomorphic Pathogenic Variants in TAF13 Are Associated with Autosomal-Recessive Intellectual Disability and Microcephaly. Am J Hum Genet. 2017 Mar 2;100(3):555-561. doi: 10.1016/j.ajhg.2017.01.032.
• [14] Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish. Brain. 2019 Mar 1;142(3):574-585. doi: 10.1093/brain/awz004.
• [15] STIL microcephaly mutations interfere with APC/C-mediated degradation and cause centriole amplification.Curr Biol. 2014 Feb 17;24(4):351-60. doi: 10.1016/j.cub.2013.12.016. Epub 2014 Jan 30.
• [16] Kinetochore KMN network gene CASC5 mutated in primary microcephaly. Hum Mol Genet. 2012 Dec 15;21(24):5306-17. doi: 10.1093/hmg/dds386. Epub 2012 Sep 13.
• [17] Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype. Clin Genet. 2014 Sep;86(3):220-8. doi: 10.1111/cge.12301. Epub 2013 Nov 18.