Kanai Masayo, Numakura Chikahiko, Sasaki Ayako, Shirahata Emi, Akaba Kazuhiro, Hashimoto Motoya, Hasegawa Hisaya, Shirasawa Senji, Hayasaka Kiyoshi
Department of Pediatrics, Yamagata University School of Medicine, Japan.
Tohoku J Exp Med. 2002 Apr;196(4):241-6. doi: 10.1620/tjem.196.241.
Recently, a few genetic abnormalities were identified in congenital central hypoventilation syndrome (CCHS or Ondine's curse). CCHS is often associated with other neurocristopathies, especially with Hirschsprung's disease (HSCR). Mutations of the genes involved in the receptor tyrosine kinase RET (REarranged during Transfection) (RET)-glial cell line-derived neurotrophic factor (GDNF) and/or endothelin 3 (EDN3)-endothelin receptor-B (EDNRB) signaling pathway have been found in some of HSCR patients. In this study, we analyzed candidates for HSCR, namely the RET, GDNF, EDN3 and EDNRB genes in three isolated CCHS patients to confirm the hypothesis that some CCHS patients have a common genetic abnormality with patients having HSCR or other neurocristopathies. We found a novel R114H mutation of the RET gene in one patient. The R114H mutation is unlikely to be a polymorphism and appears to be associated with CCHS. In addition, we also examined the HOX11L2 (RNX) gene, for which knock-out mice showed CCHS-like syndrome in these isolated CCHS patients and did not detected any mutation. Further cases should be analyzed for more candidates to clarify the pathophysiology of CCHS.
最近，在先天性中枢性低通气综合征（CCHS或翁丁氏诅咒）中发现了一些基因异常。CCHS常与其他神经嵴病变相关，尤其是与先天性巨结肠（HSCR）有关。在一些HSCR患者中发现了参与受体酪氨酸激酶RET（转染期间重排）（RET）-胶质细胞系源性神经营养因子（GDNF）和/或内皮素3（EDN3）-内皮素受体B（EDNRB）信号通路的基因突变。在本研究中，我们分析了HSCR的候选基因，即3例孤立性CCHS患者中的RET、GDNF、EDN3和EDNRB基因，以证实某些CCHS患者与HSCR或其他神经嵴病变患者存在共同基因异常这一假说。我们在1例患者中发现了RET基因的一个新的R114H突变。R114H突变不太可能是一种多态性，似乎与CCHS相关。此外，我们还检测了HOX11L2（RNX）基因，敲除该基因的小鼠在这些孤立性CCHS患者中表现出CCHS样综合征，但未检测到任何突变。需要分析更多病例的更多候选基因，以阐明CCHS的病理生理学。
