Human Disease Model Report: microcephaly 1, primary, autosomal recessive

General Information

Name

microcephaly 1, primary, autosomal recessive

FlyBase ID

FBhh0000327

Disease Ontology Term

primary autosomal recessive microcephaly 1

Parent Disease

microcephaly, primary

OMIM

MICROCEPHALY 1, PRIMARY, AUTOSOMAL RECESSIVE; MCPH1

Overview

This report describes microcephaly 1, primary, autosomal recessive (MCPH1), which is a subtype of primary microcephaly. The human gene implicated in this disease is Microcephalin 1 (MCPH1), which encodes a DNA damage response protein. There is a single fly ortholog, Dmel\MCPH1, for which for RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.

The human MCPH1 gene has not been introduced into flies.

Animals that are homozygous for a loss-of-function allele of Dmel\MCPH1 are female sterile due to an early maternal-effect lethal phenotype in which abnormal nuclear division is observed at the earliest embryonic stages, including cell cycle arrest in a metaphase-like stage; normal nuclear migration to form the syncytial blastoderm does not occur. Genetic interactions for Dmel\MCPH1 have been described; see the gene report for MCPH1.

[updated June 2016 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: microcephaly, primary

Symptoms and phenotype

Primary microcephaly (MCPH) refers to the clinical finding of a head circumference less than 3 standard deviations below the age- and sex-related mean, present at birth. Primary microcephaly is a static developmental anomaly, distinguished from secondary microcephaly, which refers to a progressive neurodegenerative condition. Microcephaly is a disorder of fetal brain growth; individuals with microcephaly have small brains and almost always have mental retardation; additional clinical features may include short stature or mild seizures (review by Woods et al., 2005; pubmed:15806441). [from MIM:251200; 2016.06.16]

(OMIM, 2013-)

Specific Disease Summary: microcephaly 1, primary, autosomal recessive

OMIM report

[MICROCEPHALY 1, PRIMARY, AUTOSOMAL RECESSIVE; MCPH1](https://omim.org/entry/251200)

Human gene(s) implicated

[MICROCEPHALIN 1; MCPH1](https://omim.org/entry/607117)

Symptoms and phenotype

See general description of primary microcephaly, above.

(OMIM, 2013-)

Genetics

MCPH1 is caused by homozygous mutation in the gene encoding microcephalin; MCPH1 is the symbol for both the disease and the gene. [from MIM:251200; 2016.06.16]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

Microcephalin 1 (MCPH1) encodes a DNA damage response protein that may play a role in G2/M checkpoint arrest. [Gene cards, MCPH1; 2016.06.21]

(FlyBase Curators, 2013-)

The MCPH1 gene encodes a regulator of chromosome condensation (Trimborn et al., 2004; pubmed:15199523). [from MIM:607117; 2016.06.16]

(OMIM, 2013-)

External links

Gene2Function (human gene): MCPH1
Gene Cards: MCPH1
MedlinePlus (gene): MCPH1
MARRVEL (human gene): MCPH1
NCBI MedGen: Primary autosomal recessive microcephaly 1 (MCPH1)
NCBI (Entrez) gene: MCPH1; microcephalin 1

Disease synonyms

MCPH1

primary microcephaly 1

Related Diseases

Related human health report(s)

Related Specific Diseases

OMIM phenotypic series

Microcephaly, primary autosomal recessive

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[MCPH1](https://omim.org/entry/251200)

[MCPH1](https://omim.org/entry/607117)

microcephaly 1, primary, autosomal recessive

[MCPH2](https://omim.org/entry/604317)

[WDR62](https://omim.org/entry/613583)

microcephaly 2, primary, autosomal recessive

[MCPH3](https://omim.org/entry/604804)

[CDK5RAP2](https://omim.org/entry/608201)

microcephaly 3, primary, autosomal recessive

[MCPH4](https://omim.org/entry/604321)

[KNL1](https://omim.org/entry/609173)

[MCPH5](https://omim.org/entry/608716)

[ASPM](https://omim.org/entry/605481)

microcephaly 5, primary, autosomal recessive

[MCPH6](https://omim.org/entry/608393)

[CENPJ](https://omim.org/entry/609279)

microcephaly 6, primary, autosomal recessive

[MCPH7](https://omim.org/entry/612703)

[STIL](https://omim.org/entry/181590)

[MCPH8](https://omim.org/entry/614673)

[CEP135](https://omim.org/entry/611423)

[MCPH9](https://omim.org/entry/614852)

[CEP152](https://omim.org/entry/613529)

[MCPH10](https://omim.org/entry/615095)

[ZNF335](https://omim.org/entry/610827)

[MCPH11](https://omim.org/entry/615414)

[PHC1](https://omim.org/entry/602978)

[MCPH12](https://omim.org/entry/616080)

[CDK6](https://omim.org/entry/603368)

[MCPH13](https://omim.org/entry/616051)

[CENPE](https://omim.org/entry/117143)

[MCPH14](https://omim.org/entry/616402)

[SASS6](https://omim.org/entry/609321)

[MCPH16](https://omim.org/entry/616681)

[ANKLE2](https://omim.org/entry/616062)

microcephaly 16, primary, autosomal recessive

[MCPH17](https://omim.org/entry/617090)

[CIT](https://omim.org/entry/605629)

microcephaly 17, primary, autosomal recessive

[MCPH18](https://omim.org/entry/617520)

[WDFY3](https://omim.org/entry/617485)

microcephaly 18, primary, autosomal dominant

[MCPH19](https://omim.org/entry/617800)

[COPB2](https://omim.org/entry/606990)

[MCPH20](https://omim.org/entry/617914)

[KIF14](https://omim.org/entry/611279)

[MCPH21](https://omim.org/entry/617983)

[NCAPD2](https://omim.org/entry/615638)

[MCPH22](https://omim.org/entry/617984)

[NCAPD3](https://omim.org/entry/609276)

[MCPH23](https://omim.org/entry/617985)

[NCAPH](https://omim.org/entry/602332)

[MCPH24](https://omim.org/entry/618179)

[NUP37](https://omim.org/entry/609264)

[MCPH25](https://omim.org/entry/618351)

[TRAPPC14](https://omim.org/entry/618350)

[NEDMISBA](https://omim.org/entry/616486)

[MFSD2A](https://omim.org/entry/614397)

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

MCPH1; microcephalin 1

D. melanogaster ortholog (based on DIOPT)

Dmel\MCPH1

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\MCPH1

Gene Snapshot

Microcephalin (MCPH1) encodes a BRCT domain-containing protein that acts in genome stability and cell cycle regulation. It is required to co-ordinate centrosome and nuclear division during rapid syncitial embryonic cell divisions. [Date last reviewed: 2019-02-28]

Molecular function (GO)

Cellular component (GO)