title: Identification of microcephalin, a protein implicated in determining the size of the human brain.
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.
authors.affiliation: Molecular Medicine Unit, University of Leeds, United Kingdom. medapj@leeds.ac.uk
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Jackson
authors.forename: Helen
authors.initials: H
authors.lastname: Eastwood
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Bell
authors.forename: Jimi
authors.initials: J
authors.lastname: Adu
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
authors.forename: Ian M
authors.initials: IM
authors.lastname: Carr
authors.forename: Emma
authors.initials: E
authors.lastname: Roberts
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hampshire
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Mighell
authors.forename: Gulshan
authors.initials: G
authors.lastname: Karbani
authors.forename: Hussain
authors.initials: H
authors.lastname: Jafri
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Rashid
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mueller
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Markham
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Woods
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000033:anatomy & histology* / Q000473:pathology; D018797:Cell Cycle Proteins; D002648:Child; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009929:Organ Size / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D004247:DNA