Identification of microcephalin, a protein implicated in determining the size of the human brain
Open accessAbstract
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.
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Microcephaly is largely caused by mutations disrupting genes encoding centrosomal proteins: MCPH1, ASPM, CDK5RAP2, CENPJ, STIL, WDR62, CEP152, and CEP63.
“Microcephaly is largely caused by mutations that disrupt genes encoding centrosomal proteins: MCPH1, ASPM, CDK5RAP2, CENPJ, STIL, WDR62, CEP152, and CEP63 (Bilguvar et al., 2010; Bond et al., 2002; Bond et al., 2005; Guernsey et al., 2010; Jackson et al., 2002; Kumar et al., 2009; Nicholas et al., 2010; Sir et al., 2011; Yu et al., 2010).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Jackson et al., 2002
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- Authors
- Jackson, A. P., Eastwood, H., Bell, S. M., Adu, J., Toomes, C., Carr, I. M., Roberts, E., Hampshire, D. J., Crow, Y. J., Mighell, A. J., Karbani, G., Jafri, H., Rashid, Y., Mueller, R. F., Markham, A. F., & Woods, C. G.
- Affiliations
- University of Leeds (GB)
- St James's University Hospital (GB)
- Corresponding author
- Jackson, Andrew P.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 71
- Issue
- 1
- Pages
- 136-142
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC419993
- OpenAlex
- W2166489903
- Cited by
- 482
- References
- 22
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 5 · 2022: 22 · 2021: 12 · 2020: 17 · 2019: 13 · 2018: 10 · 2017: 26 · 2016: 23 · 2015: 17 · 2014: 20 · 2013: 22 · 2012: 29
- FWCI
- 10.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion)
- University of Brighton Repository (University of Brighton) (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microcephalin, MCPH1, primary microcephaly, haplotypes, cortical development, brain size, autosomal recessive neurodevelopmental disorder, fetal brain
- MeSH terms
- Adolescent, Adult, Amino Acid Sequence, Animals, Base Sequence, Brain, Child, Chromosomes, Human, Pair 8, Cloning, Molecular, Cytoskeletal Proteins, DNA, DNA Mutational Analysis, Female, Embryonic and Fetal Development, Humans, Male, Microcephaly, Molecular Sequence Data, Nerve Tissue Proteins, Organ Size, RNA, Messenger, Sequence Homology, Amino Acid, In Situ Hybridization, Gene Expression Regulation, Developmental, Cell Cycle Proteins, Mice
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