KIF21A mutations in two Chinese families with congenital fibrosis of the extraocular muscles (CFEOM).
OBJECTIVE
Two Chinese families (XT and YT) with congenital fibrosis of the extraocular muscles (CFEOM) were identified. The purpose of this study was to determine if previously described Homo sapiens kinesin family member 21A (KIF21A) mutations were responsible for CFEOM in these two Chinese pedigrees.


METHODS
Clinical characterization and genetic studies were performed. Microsatellite genotyping for linkage to the CFEOM1 and CFEOM3 loci was performed. The probands were screened for KIF21A mutations by bidirectional direct sequencing. Once a mutation was detected in the proband, all other participating family members and 100 unrelated control normal individuals were screened for the mutation.


RESULTS
All affected individuals in family XT shared the common manifestations of CFEOM1. Family YT had two affected individuals, a mother and a daughter. The daughter had CFEOM1, while her mother never had congential ptosis but did have limited extraocular movements status post strabismus surgery. Haplotype analysis revealed that pedigree XT was linked to the 12q CFEOM1 locus and the affected memberes harbored the second most common missense mutation in KIF21A (2,861G>A, R954Q). Family YT harbored the most common missense de novo mutation in KIF21A (2,860C>T, R954W). Both of these mutations have been previously described.


CONCLUSIONS
The observation of these two KIF21A mutations in a Chinese pedigree underscores the homogeneity of these mutations as a cause of CFEOM1 and CFEOM3 across ethnic divisions.
Department of Ophthalmology, Medical College of Qingdao University, the Affiliated Hospital of Medical College Qingdao University, Qingdao, Shandong Province, China. yangxian_70@yahoo.com.cn
Xian
X
Yang
Koki
K
Yamada
Bradley
B
Katz
Hongzai
H
Guan
Lifei
L
Wang
Caroline
C
Andrews
Guiqiu
G
Zhao
Elizabeth C
EC
Engle
Haoyu
H
Chen
Zongzhong
Z
Tong
Jie
J
Kong
Cong
C
Hu
Qinglan
Q
Kong
Guiyun
G
Fan
Ze
Z
Wang
Meizhen
M
Ning
Shaoyan
S
Zhang
Jinling
J
Xu
Kang
K
Zhang
D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D004252:DNA Mutational Analysis; D005133:Eye Movements / Q000235:genetics; D005190:Family; D005260:Female; D005355:Fibrosis; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D015835:Ocular Motility Disorders / Q000151:congenital* / Q000235:genetics* / Q000503:physiopathology; D009801:Oculomotor Muscles / Q000473:pathology* / Q000503:physiopathology; D010375:Pedigree
C119023:KIF21A protein, human; D016547:Kinesins