This report describes microcephaly 2, primary, autosomal recessive (MCPH2), which is a subtype of primary microcephaly. The human gene implicated in this disease is WD Repeat Domain 62 (WDR62), which encodes a protein is associated with the mitotic spindle pole in dividing neural cells. There is a single fly ortholog, Dmel\Wdr62, for which amorphic mutations, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\Wdr62 is orthologous to a second human gene, MAPKBP1.
The human WDR62 gene has not been introduced into flies.
Animals that are homozygous or hemizygous for amorphic alleles of Dmel\Wdr62 exhibit reduced viability, with 50-75% dying during the late pupal stage. In third instar neuroblasts abnormal mitoses are observed, including loss of microtubule-organizing center activity on the apical centrosome during interphase and other centrosome abnormalities. Third instar larval brains are significantly smaller compared to wild type, with significantly reduced neuroblast numbers and significantly increased cell cycle length.
[updated June 2016 by FlyBase; FBrf0222196]
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]
[MICROCEPHALY 2, PRIMARY, AUTOSOMAL RECESSIVE, WITH OR WITHOUT CORTICAL MALFORMATIONS; MCPH2](https://omim.org/entry/604317)
[WD REPEAT-CONTAINING PROTEIN 62; WDR62](https://omim.org/entry/613583)
See general description of primary microcephaly, above.
MCPH2 is caused by homozygous or compound heterozygous mutation in the WDR62 gene. [from MIM:604317; 2016.06.16]
The protein encoded by WDR62 is proposed to play a role in cerebral cortical development, affecting neuronal proliferation and migration. [from Gene Cards, WDR62; 2016.06.22]
The WDR62 protein is associated with the mitotic spindle pole; it may be restricted to neural precursors undergoing mitosis. [Nicholas, et al., 2010; pubmed:20890279]
Many to one: 2 human to 1 Drosophila; additional orthologous human gene is MAPKBP1.
High-scoring ortholog of human genes WDR62 and MAPKBP1 (1 Drosophila to 2 human). Dmel\Wdr62 shares 33-34% identity and 46-49% similarity with the human genes.
