Microcephalin

microcephaly, primary autosomal recessive 1
Crystallographic structure of the N-terminal BRCT domain of human microcephalin (MCPH1)
Identifiers
Symbol	MCPH1
Alt. symbols	Microcephalin, BRIT1
Entrez	79648
HUGO	6954
OMIM	607117
UniProt	Q8NEM0
Other data
Locus	Chr. 8 p23

Microcephalin (MCPH1) is a gene that is expressed during fetal brain development. Certain mutations in MCPH1, when homozygous, cause primary microcephaly — a severely diminished brain. Hence it has been assumed that variants have a role in brain development, but in normal individuals no effect on mental ability or behavior has yet been demonstrated in either this or another similarly studied microcephaly gene, ASPM. However, an association has been established between normal variation in brain structure as measured with MRI (i.e., primarily cortical surface area and total brain volume) and common genetic variants within both the MCPH1 gene and another similarly studied microcephaly gene, CDK5RAP2.

Microcephalin proteins contain the following three domains:

MCPH1 is expressed in the fetal brain, in the developing forebrain, and on the walls of the lateral ventricles. Cells of this area divide, producing neurons that migrate to eventually form the cerebral cortex.

A derived form of MCPH1 called haplogroup D appeared about 37,000 years ago (any time between 14,000 and 60,000 years ago) and has spread to become the most common form of microcephalin throughout the world except Sub-Saharan Africa; this rapid spread suggests a selective sweep. However, scientists have not identified the evolutionary pressures that may have caused the spread of these mutations. This variant of the gene is thought to contribute to increased brain volume. Modern distributions of chromosomes bearing the ancestral forms of MCPH1 and ASPM are correlated with the incidence of tonal languages, but the nature of this relationship is far from clear.