A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis.
Craniosynostosis, the premature fusion of calvarial sutures, is a common developmental anomaly that causes abnormal skull shape. The locus for one autosomal dominant form of craniosynostosis has been mapped to chromosome 5qter. The human MSX2 gene localizes to chromosome 5, and a polymorphic marker in the MSX2 intron segregates in a kindred with the disorder with no recombination. Moreover, a histidine substitutes for a highly conserved proline at position 7 of the MSX2 homeodomain exclusively in affected members. In the mouse, transcripts of the Msx2 gene are localized to calvarial sutures. These results provide compelling evidence that the mutation causes this craniosynostosis syndrome.
Jabs
E W
EW
Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland 21287.
Müller
U
U
Li
X
X
Ma
L
L
Luo
W
W
Haworth
I S
IS
Klisak
I
I
Sparkes
R
R
Warman
M L
ML
Mulliken
J B
JB
D000168:Acrocephalosyndactylia / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003393:Cranial Sutures / Q000002:abnormalities; D003398:Craniosynostoses / Q000145:classification / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005796:Genes / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics*; D008040:Genetic Linkage; D018398:Homeodomain Proteins; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012333:RNA, Messenger / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D012333:RNA, Messenger