De novo mutations of SETBP1 cause Schinzel-Giedion syndrome.
Schinzel-Giedion syndrome is characterized by severe mental retardation, distinctive facial features and multiple congenital malformations; most affected individuals die before the age of ten. We sequenced the exomes of four affected individuals (cases) and found heterozygous de novo variants in SETBP1 in all four. We also identified SETBP1 mutations in eight additional cases using Sanger sequencing. All mutations clustered to a highly conserved 11-bp exonic region, suggesting a dominant-negative or gain-of-function effect.
Hoischen
Alexander
A
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
van Bon
Bregje W M
BW
Gilissen
Christian
C
Arts
Peer
P
van Lier
Bart
B
Steehouwer
Marloes
M
de Vries
Petra
P
de Reuver
Rick
R
Wieskamp
Nienke
N
Mortier
Geert
G
Devriendt
Koen
K
Amorim
Marta Z
MZ
Revencu
Nicole
N
Kidd
Alexa
A
Barbosa
Mafalda
M
Turner
Anne
A
Smith
Janine
J
Oley
Christina
C
Henderson
Alex
A
Hayes
Ian M
IM
Thompson
Elizabeth M
EM
Brunner
Han G
HG
de Vries
Bert B A
BB
Veltman
Joris A
JA
D000015:Abnormalities, Multiple / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D013577:Syndrome
D002352:Carrier Proteins; D009687:Nuclear Proteins; C425066:SETBP1 protein, human