Identification of microcephalin, a protein implicated in determining the size of the human brain.
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.
Jackson
Andrew P
AP
Molecular Medicine Unit, University of Leeds, United Kingdom. medapj@leeds.ac.uk
Eastwood
Helen
H
Bell
Sandra M
SM
Adu
Jimi
J
Toomes
Carmel
C
Carr
Ian M
IM
Roberts
Emma
E
Hampshire
Daniel J
DJ
Crow
Yanick J
YJ
Mighell
Alan J
AJ
Karbani
Gulshan
G
Jafri
Hussain
H
Rashid
Yasmin
Y
Mueller
Robert F
RF
Markham
Alexander F
AF
Woods
C Geoffrey
CG
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
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D004247:DNA