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Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type

Authors
 Byung-Joo Min  ;  Namshin Kim  ;  Taesu Chung  ;  Ok-Hwa Kim  ;  Gen Nishimura  ;  Chin Youb Chung  ;  Hae Ryong Song  ;  Hyun Woo Kim  ;  Hye Ran Lee  ;  Jiwoong Kim  ;  Tae-Hoon Kang  ;  Myung-Eui Seo  ;  San-Deok Yang  ;  Do-Hwan Kim  ;  Seung-Bok Lee  ;  Jong-Il Kim  ;  Jeong-Sun Seo  ;  Ji-Yeob Choi  ;  Daehee Kang  ;  Dongsup Kim  ;  Woong-Yang Park  ;  Tae-Joon Cho 
Citation
 AMERICAN JOURNAL OF HUMAN GENETICS, Vol.89(6) : 760-766, 2011 
Journal Title
AMERICAN JOURNAL OF HUMAN GENETICS
ISSN
 0002-9297 
Issue Date
2011
MeSH
Abnormalities, Multiple/genetics* ; Adolescent ; Amino Acid Motifs ; Animals ; Case-Control Studies ; Child ; Child, Preschool ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics* ; Exome* ; Female ; Gene Expression ; Genetic Association Studies ; Genotype ; Humans ; Joint Dislocations/congenital* ; Joint Dislocations/genetics ; Joint Instability/genetics* ; Kinesin/chemistry ; Kinesin/genetics* ; Male ; Mice ; Middle Aged ; Molecular Dynamics Simulation ; Mutation, Missense* ; Organ Specificity ; Osteochondrodysplasias/genetics* ; Pedigree ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA*
Abstract
Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL), leptodactylic (lepto-SEMDJL) or Hall type, is an autosomal-dominant skeletal dysplasia manifesting with short stature, joint laxity with dislocation(s), limb malalignment, and spinal deformity. Its causative gene mutation has not yet been discovered. We captured and sequenced the exomes of eight affected individuals in six unrelated kindreds (three individuals in a family and five simplex individuals). Five novel sequence variants in KIF22, which encodes a member of the kinesin-like protein family, were identified in seven individuals. Sanger sequencing of KIF22 confirmed that c.443C>T (p.Pro148Ser) cosegregated with the phenotype in the affected individuals in the family; c.442C>T (p.Pro148Leu) or c.446G>A (p.Arg149Gln) was present in four of five simplex individuals, but was absent in unaffected individuals in their family and 505 normal cohorts. KIF22 mRNA was detected in human bone, cartilage, joint capsule, ligament, skin, and primary cultured chondrocytes. In silico analysis of KIF22 protein structure indicates that Pro148 and Arg149 are important in maintaining hydrogen bonds in the ATP binding and motor domains of KIF22. We conclude that these mutations in KIF22 cause lepto-SEMDJL.
Files in This Item:
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DOI
10.1016/j.ajhg.2011.10.015
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyun Woo(김현우) ORCID logo https://orcid.org/0000-0001-8576-1877
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94784
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