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Identification of microcephalin, a protein implicated in determining the size of the human brain
Andrew P Jackson1, Helen Eastwood, Sandra M Bell
1Molecular Medicine Unit, University of Leeds, United Kingdom. medapj@leeds.ac.uk
Abstract:
Primary microcephaly (MIM 251200) is an autosomal recessive neurodevelopmental condition in which there is a global reduction in cerebral cortex volume, to a size comparable with that of early hominids. We previously mapped the MCPH1 locus, for primary microcephaly, to chromosome 8p23, and here we report that a gene within this interval, encoding a BRCA1 C-terminal domain-containing protein, is mutated in MCPH1 families sharing an ancestral 8p23 haplotype. This gene, microcephalin, is expressed in the developing cerebral cortex of the fetal brain. Further study of this and related genes may provide important new insights into neocortical development and evolution.
Insights
Primary microcephaly, a neurodevelopmental disorder causing reduced brain size, is linked to mutations in the microcephalin gene. This finding offers insights into brain development and evolution.
Area of Science:
- Genetics
- Neuroscience
- Evolutionary Biology
Background:
- Primary microcephaly is an autosomal recessive neurodevelopmental condition.
- Characterized by a significant reduction in cerebral cortex volume.
- Previous research mapped the primary microcephaly locus (MCPH1) to chromosome 8p23.
Purpose of the Study:
- To identify the specific gene responsible for primary microcephaly within the mapped MCPH1 locus.
- To investigate the role of this gene in human brain development and evolution.
Main Methods:
- Genetic linkage analysis to identify the disease locus.
- Mutation screening within candidate genes in the 8p23 region.
- Expression analysis of the identified gene in fetal brain tissue.
Main Results:
- A gene encoding a BRCA1 C-terminal domain-containing protein, named microcephalin, was identified within the MCPH1 locus.
- Mutations in microcephalin were found in families with primary microcephaly who share an ancestral haplotype.
- Microcephalin is expressed in the developing fetal cerebral cortex.
Conclusions:
- Mutations in the microcephalin gene cause primary microcephaly.
- This discovery provides a molecular basis for understanding neocortical development.
- Further research into microcephalin and related genes may illuminate human brain evolution.