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

33 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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Min, B. J., Kim, N., Chung, T., Kim, O. H., Nishimura, G., Chung, C. Y., Song, H. R., Kim, H. W., Lee, H. R., Kim, J., Kang, T. H., Seo, M. E., Yang, S. D., Kim, D. H., Lee, S. B., Kim, J. I., Seo, J. S., Choi, J. Y., Kang, D., ... Cho, T. J. (2011). Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type. American Journal of Human Genetics, 89(6), 760-766. https://doi.org/10.1016/j.ajhg.2011.10.015