Mutations in CD96, a member of the immunoglobulin superfamily, cause a form of the C (Opitz trigonocephaly) syndrome.
The C syndrome is characterized by trigonocephaly and associated anomalies, such as unusual facies, psychomotor retardation, redundant skin, joint and limb abnormalities, and visceral anomalies. In an individual with the C syndrome who harbors a balanced chromosomal translocation, t(3;18)(q13.13;q12.1), we discovered that the TACTILE gene for CD96, a member of the immunoglobulin superfamily, was disrupted at the 3q13.3 breakpoint. In mutation analysis of nine karyotypically normal patients given diagnoses of the C or C-like syndrome, we identified a missense mutation (839C-->T, T280M) in exon 6 of the CD96 gene in one patient with the C-like syndrome. The missense mutation was not found among 420 unaffected Japanese individuals. Cells with mutated CD96 protein (T280M) lost adhesion and growth activities in vitro. These findings indicate that CD96 mutations may cause a form of the C syndrome by interfering with cell adhesion and growth.
Kaname
Tadashi
T
Department of Medical Genetics, University of the Ryukyus Faculty of Medicine, Nishihara, Okinawa, Japan. tkaname@med.u-ryukyu.ac.jp
Yanagi
Kumiko
K
Chinen
Yasutsugu
Y
Makita
Yoshio
Y
Okamoto
Nobuhiko
N
Maehara
Hiroki
H
Owan
Ichiro
I
Kanaya
Fuminori
F
Kubota
Yoshiaki
Y
Oike
Yuichi
Y
Yamamoto
Toshiyuki
T
Kurosawa
Kenji
K
Fukushima
Yoshimitsu
Y
Bohring
Axel
A
Opitz
John M
JM
Yoshiura
Ko-Ichiro
K
Niikawa
Norio
N
Naritomi
Kenji
K
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D002448:Cell Adhesion / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D013577:Syndrome; D014178:Translocation, Genetic
D015703:Antigens, CD; C116131:CD96 antigen; D017931:DNA Primers