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.
Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, USA.
K
K
Gaudenz
E
E
Roessler
N
N
Quaderi
B
B
Franco
G
G
Feldman
D L
DL
Gasser
B
B
Wittwer
J
J
Horst
E
E
Montini
J M
JM
Opitz
A
A
Ballabio
M
M
Muenke
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