Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).
Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.
Yamada
Koki
K
Department of Medicine (Genetics), Enders 5, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Andrews
Caroline
C
Chan
Wai-Man
WM
McKeown
Craig A
CA
Magli
Adriano
A
de Berardinis
Teresa
T
Loewenstein
Anat
A
Lazar
Moshe
M
O'Keefe
Michael
M
Letson
Robert
R
London
Arnold
A
Ruttum
Mark
M
Matsumoto
Naomichi
N
Saito
Nakamichi
N
Morris
Lisa
L
Del Monte
Monte
M
Johnson
Roger H
RH
Uyama
Eiichiro
E
Houtman
Willem A
WA
de Vries
Berendina
B
Carlow
Thomas J
TJ
Hart
Blaine L
BL
Krawiecki
Nicolas
N
Shoffner
John
J
Vogel
Marlene C
MC
Katowitz
James
J
Goldstein
Scott M
SM
Levin
Alex V
AV
Sener
Emin C
EC
Ozturk
Banu T
BT
Akarsu
A Nurten
AN
Brodsky
Michael C
MC
Hanisch
Frank
F
Cruse
Robert P
RP
Zubcov
Alina A
AA
Robb
Richard M
RM
Roggenkäemper
Peter
P
Gottlob
Irene
I
Kowal
Lionel
L
Battu
Ravi
R
Traboulsi
Elias I
EI
Franceschini
Piergiorgio
P
Newlin
Anna
A
Demer
Joseph L
JL
Engle
Elizabeth C
EC
D000595:Amino Acid Sequence; D002648:Child; D005260:Female; D005355:Fibrosis; D008040:Genetic Linkage; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009801:Oculomotor Muscles / Q000473:pathology*; D009886:Ophthalmoplegia / Q000151:congenital* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017386:Sequence Homology, Amino Acid
C119023:KIF21A protein, human; D009419:Nerve Tissue Proteins; D016547:Kinesins