Opitz G/BBB syndrome in Xp22: mutations in the MID1 gene cluster in the carboxy-terminal domain.
The MID1 gene in Xp22 codes for a novel member of proteins containing a RING finger, B-box, coiled-coil and a conserved C-terminal domain. Initially, three mutations in the C-terminal region were found in patients with Opitz G/BBB syndrome, a defect of midline development. Here we have determined the complete gene structure of the MID1 gene and have analyzed all nine exons for mutations in a set of 40 unrelated Opitz G/BBB patients. We now report six additional mutations all clustered in the carboxy-terminal domain of the MID1 protein. These data suggest that this conserved domain of the B-box proteins may play a fundamental role in the pathogenesis of Opitz syndrome and in morphogenetic events at the midline during blastogenesis.
Gaudenz
K
K
Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, USA.
Roessler
E
E
Quaderi
N
N
Franco
B
B
Feldman
G
G
Gasser
D L
DL
Wittwer
B
B
Horst
J
J
Montini
E
E
Opitz
J M
JM
Ballabio
A
A
Muenke
M
M
D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008868:Microtubule Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D009687:Nuclear Proteins; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D014960:X Chromosome; D016335:Zinc Fingers
D008868:Microtubule Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases