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.
Department of Medicine (Genetics), Enders 5, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Koki
K
Yamada
Caroline
C
Andrews
Wai-Man
WM
Chan
Craig A
CA
McKeown
Adriano
A
Magli
Teresa
T
de Berardinis
Anat
A
Loewenstein
Moshe
M
Lazar
Michael
M
O'Keefe
Robert
R
Letson
Arnold
A
London
Mark
M
Ruttum
Naomichi
N
Matsumoto
Nakamichi
N
Saito
Lisa
L
Morris
Monte
M
Del Monte
Roger H
RH
Johnson
Eiichiro
E
Uyama
Willem A
WA
Houtman
Berendina
B
de Vries
Thomas J
TJ
Carlow
Blaine L
BL
Hart
Nicolas
N
Krawiecki
John
J
Shoffner
Marlene C
MC
Vogel
James
J
Katowitz
Scott M
SM
Goldstein
Alex V
AV
Levin
Emin C
EC
Sener
Banu T
BT
Ozturk
A Nurten
AN
Akarsu
Michael C
MC
Brodsky
Frank
F
Hanisch
Robert P
RP
Cruse
Alina A
AA
Zubcov
Richard M
RM
Robb
Peter
P
Roggenkäemper
Irene
I
Gottlob
Lionel
L
Kowal
Ravi
R
Battu
Elias I
EI
Traboulsi
Piergiorgio
P
Franceschini
Anna
A
Newlin
Joseph L
JL
Demer
Elizabeth C
EC
Engle
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