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Molecular analysis of congenital central hypoventilation syndrome

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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.

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Acknowledgements

We thank Prof. Y. Matsubara for helpful comments and discussions.

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Authors and Affiliations

  1. Department of Pediatrics, Yamagata Univercity School of Medicine, 2-2-2 Iida-nishi, 990-9585, Yamagata, Japan

    Ayako Sasaki, Masayo Kanai, Kazuki Kijima, Kazuhiro Akaba & Kiyoshi Hayasaka

  2. Department of Neonatal Intensive Care Unit, Saiseikai Yamagata Saisei Hospital, Yamagata, Japan

    Motoya Hashimoto

  3. Department of Neonatology, Matsudo City Hospital, Matsudo, Chiba, Japan

    Hisaya Hasegawa

  4. Department of Pediatrics, Yamagata Prefectual Nihonkai Hospital, Yamagata, Japan

    Shinsuke Otaki

  5. Department of Neonatology, Gunma Children’s Medical Center, Gunma, Japan

    Takenobu Koizumi

  6. Department of Neonatology, Osaka City General Hospital, Osaka, Japan

    Satoshi Kusuda

  7. Department of Pediatrics, Nagaoka Red Cross Hospital, Niigata, Japan

    Youhei Ogawa

  8. Department of Pediatrics and Neonatology, Japan Red Cross Medical Center, Tokyo, Japan

    Keiji Tuchiya & Wakako Yamamoto

  9. Perinatal Center and Division of Clinical Pathology, Nagano Children’s Hospital, Nagano, Japan

    Tomohiko Nakamura

Authors
  1. Ayako Sasaki
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  2. Masayo Kanai
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  3. Kazuki Kijima
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  4. Kazuhiro Akaba
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  5. Motoya Hashimoto
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  6. Hisaya Hasegawa
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  7. Shinsuke Otaki
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  8. Takenobu Koizumi
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  9. Satoshi Kusuda
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  10. Youhei Ogawa
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  11. Keiji Tuchiya
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  12. Wakako Yamamoto
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  13. Tomohiko Nakamura
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  14. Kiyoshi Hayasaka
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Corresponding author

Correspondence to Kiyoshi Hayasaka.

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Sasaki, A., Kanai, M., Kijima, K. et al. Molecular analysis of congenital central hypoventilation syndrome. Hum Genet 114, 22–26 (2003). https://doi.org/10.1007/s00439-003-1036-z

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  • DOI: https://doi.org/10.1007/s00439-003-1036-z

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