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

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 KimWoong Yang Park, Tae Joon Cho

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)760-766
Number of pages7
JournalAmerican Journal of Human Genetics
Volume89
Issue number6
DOIs
Publication statusPublished - 2011 Dec 9

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Exome
Mutation
Joint Capsule
Joint Instability
Kinesin
Chondrocytes
Ligaments
Computer Simulation
Cartilage
Hydrogen
Proteins
Extremities
Adenosine Triphosphate
Phenotype
Bone and Bones
Messenger RNA
Skin
Genes
Spondyloepimetaphyseal Dysplasia With Joint Laxity

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type. / Min, Byung Joo; Kim, Namshin; Chung, Taesu; Kim, Ok Hwa; Nishimura, Gen; Chung, Chin Youb; Song, Hae Ryong; Kim, Hyun Woo; Lee, Hye Ran; Kim, Jiwoong; Kang, Tae Hoon; Seo, Myung Eui; Yang, San Deok; Kim, Do Hwan; Lee, Seung Bok; Kim, Jong Il; Seo, Jeong Sun; Choi, Ji Yeob; Kang, Daehee; Kim, Dongsup; Park, Woong Yang; Cho, Tae Joon.

In: American Journal of Human Genetics, Vol. 89, No. 6, 09.12.2011, p. 760-766.

Research output: Contribution to journalArticle

Min, BJ, Kim, N, Chung, T, Kim, OH, Nishimura, G, Chung, CY, Song, HR, Kim, HW, Lee, HR, Kim, J, Kang, TH, Seo, ME, Yang, SD, Kim, DH, Lee, SB, Kim, JI, Seo, JS, Choi, JY, Kang, D, Kim, D, Park, WY & Cho, TJ 2011, 'Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type', American Journal of Human Genetics, vol. 89, no. 6, pp. 760-766. https://doi.org/10.1016/j.ajhg.2011.10.015
Min, Byung Joo ; Kim, Namshin ; Chung, Taesu ; Kim, Ok Hwa ; Nishimura, Gen ; Chung, Chin Youb ; Song, Hae Ryong ; Kim, Hyun Woo ; Lee, Hye Ran ; Kim, Jiwoong ; Kang, Tae Hoon ; Seo, Myung Eui ; Yang, San Deok ; Kim, Do Hwan ; Lee, Seung Bok ; Kim, Jong Il ; Seo, Jeong Sun ; Choi, Ji Yeob ; Kang, Daehee ; Kim, Dongsup ; Park, Woong Yang ; Cho, Tae Joon. / Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type. In: American Journal of Human Genetics. 2011 ; Vol. 89, No. 6. pp. 760-766.
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T1 - Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type

AU - Min, Byung Joo

AU - Kim, Namshin

AU - Chung, Taesu

AU - Kim, Ok Hwa

AU - Nishimura, Gen

AU - Chung, Chin Youb

AU - Song, Hae Ryong

AU - Kim, Hyun Woo

AU - Lee, Hye Ran

AU - Kim, Jiwoong

AU - Kang, Tae Hoon

AU - Seo, Myung Eui

AU - Yang, San Deok

AU - Kim, Do Hwan

AU - Lee, Seung Bok

AU - Kim, Jong Il

AU - Seo, Jeong Sun

AU - Choi, Ji Yeob

AU - Kang, Daehee

AU - Kim, Dongsup

AU - Park, Woong Yang

AU - Cho, Tae Joon

PY - 2011/12/9

Y1 - 2011/12/9

N2 - 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.

AB - 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.

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