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CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant
  1. Tatsuya Furuichi1,2,
  2. Jin Dai1,
  3. Tae-Joon Cho3,
  4. Satoru Sakazume4,
  5. Masahide Ikema5,
  6. Yoshito Matsui6,
  7. Gareth Baynam7,
  8. Toshiro Nagai4,
  9. Noriko Miyake8,
  10. Naomichi Matsumoto8,
  11. Hirofumi Ohashi9,
  12. Sheila Unger10,
  13. Andrea Superti-Furga10,
  14. Ok-Hwa Kim11,
  15. Gen Nishimura12,
  16. Shiro Ikegawa1
  1. 1Laboratory of Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan
  2. 2Laboratory Animal Facility, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan
  3. 3Department of Orthopaedic Surgery, Seoul National University Children's Hospital, Seoul, Korea
  4. 4Department of Pediatrics, Dokkyo Medical University Kosigaya Hospital, Koshigaya, Japan
  5. 5Department of Orthopaedic, Nagasaki Prefectural Center of Medicine and Welfare for Children, Nagasaki, Japan
  6. 6Department of Orthopedic Surgery, University of Toyama, Toyama, Japan
  7. 7Genetic Services of Western Australia, Princess Margaret Hospital for Children and King Edward Memorial Hospital for Women, Western Australia, Australia
  8. 8Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  9. 9Division of Medical Genetics, Saitama Children's Medical Center, Iwatsuki, Japan
  10. 10Center for Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany
  11. 11Department of Radiology, Ajou University Hospital, Suwon, Korea
  12. 12Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Futyu, Japan
  1. Correspondence to Dr Shiro Ikegawa, Laboratory of Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; sikegawa{at}


Background Desbuquois dysplasia (DD) is a recessively inherited condition characterised by short stature, generalised skeletal dysplasia and advanced bone maturation. DD is both clinically and radiographically heterogeneous, and two subtypes have been distinguished based on the presence (type 1) or absence (type 2) of an accessory metacarpal bone. In addition, an apparently distinct variant without additional metacarpal bone but with short metacarpals and long phalanges (Kim variant) has been described recently. Mutations in the gene that encodes for CANT1 (calcium-activated nucleotidase 1) have been identified in a subset of patients with DD type 1.

Methods A series of 11 subjects with DD from eight families (one type 1, two type 2, five Kim variant) were examined for CANT1 mutations by direct sequencing of all coding exons and their flanking introns.

Results Eight distinct mutations were identified in seven families (one type 1, one type 2 and all 5 Kim variant): three were nonsense and five were missense. All missense mutations occurred at highly conserved amino acids in the nucleotidase conserved regions of CANT1. Measurement of nucleotidase activity in vitro showed that the missense mutations were all associated with loss-of-function.

Conclusion The clinical-radiographic spectrum produced by CANT1 mutations must be extended to include DD type 2 and Kim variant. While presence or absence of an additional metacarpal ossification centre has been used to distinguish subtypes of DD, this sign is not a distinctive criterion to predict the molecular basis in DD.

  • Desbuquois dysplasia
  • CANT1
  • mutation
  • nucleotidase
  • heterogeneity
  • diagnostics
  • genetics
  • cell biology

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  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Ethics Committee of RIKEN.

  • Provenance and peer review Not commissioned; externally peer reviewed.