Human Genetics

, Volume 114, Issue 1, pp 22–26

Molecular analysis of congenital central hypoventilation syndrome

  • Ayako Sasaki
  • Masayo Kanai
  • Kazuki Kijima
  • Kazuhiro Akaba
  • Motoya Hashimoto
  • Hisaya Hasegawa
  • Shinsuke Otaki
  • Takenobu Koizumi
  • Satoshi Kusuda
  • Youhei Ogawa
  • Keiji Tuchiya
  • Wakako Yamamoto
  • Tomohiko Nakamura
  • Kiyoshi Hayasaka
Original Investigation

DOI: 10.1007/s00439-003-1036-z

Cite this article as:
Sasaki, A., Kanai, M., Kijima, K. et al. Hum Genet (2003) 114: 22. doi:10.1007/s00439-003-1036-z

Abstract

Congenital central hypoventilation syndrome (CCHS or Ondine’s curse; OMIM 209880) is a disorder characterized by an idiopathic failure of the automatic control of breathing. CCHS is frequently complicated with neurocristopathies such as Hirschsprung’s disease (HSCR). The genes involved in the RET-GDNF signaling and/or EDN3-EDNRB signaling pathways have been analyzed as candidates for CCHS; however, only a few patients have mutations of the RET, EDN3, and GDNF genes. Recently, mutations of the PHOX2B gene, especially polyalanine expansions, have been detected in two thirds of patients. We studied the RET, GDNF, GFRA1, PHOX2A, PHOX2B, HASH-1, EDN1, EDN3, EDNRB, and BDNF genes in seven patients with isolated CCHS and three patients with HSCR. We detected polyalanine expansions and a novel frameshift mutation of the PHOX2B gene in four patients and one patient, respectively. We also found several mutations of the RET, GFRA1, PHOX2A, and HASH-1 genes in patients with or without mutations of the PHOX2B gene. Our study confirmed the prominent role of mutations in the PHOX2B gene in the pathogenesis of CCHS. Mutations of the RET, GFRA1, PHOX2A, and HASH-1 genes may also be involved in the pathogenesis of CCHS. To make clear the pathogenesis of CCHS, the analysis of more cases and further candidates concerned with the development of the autonomic nervous system is required.

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Ayako Sasaki
    • 1
  • Masayo Kanai
    • 1
  • Kazuki Kijima
    • 1
  • Kazuhiro Akaba
    • 1
  • Motoya Hashimoto
    • 2
  • Hisaya Hasegawa
    • 3
  • Shinsuke Otaki
    • 4
  • Takenobu Koizumi
    • 5
  • Satoshi Kusuda
    • 6
  • Youhei Ogawa
    • 7
  • Keiji Tuchiya
    • 8
  • Wakako Yamamoto
    • 8
  • Tomohiko Nakamura
    • 9
  • Kiyoshi Hayasaka
    • 1
  1. 1.Department of PediatricsYamagata Univercity School of MedicineYamagataJapan
  2. 2.Department of Neonatal Intensive Care UnitSaiseikai Yamagata Saisei HospitalYamagataJapan
  3. 3.Department of NeonatologyMatsudo City HospitalMatsudoJapan
  4. 4.Department of PediatricsYamagata Prefectual Nihonkai HospitalYamagataJapan
  5. 5.Department of NeonatologyGunma Children’s Medical CenterGunmaJapan
  6. 6.Department of NeonatologyOsaka City General HospitalOsakaJapan
  7. 7.Department of PediatricsNagaoka Red Cross HospitalNiigataJapan
  8. 8.Department of Pediatrics and NeonatologyJapan Red Cross Medical CenterTokyoJapan
  9. 9.Perinatal Center and Division of Clinical PathologyNagano Children’s HospitalNaganoJapan

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