title: Congenital central hypoventilation syndrome: a novel mutation of the RET gene in an isolated case.
abstract: 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.
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Kanai
authors.forename: Chikahiko
authors.initials: C
authors.lastname: Numakura
authors.forename: Ayako
authors.initials: A
authors.lastname: Sasaki
authors.forename: Emi
authors.initials: E
authors.lastname: Shirahata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Akaba
authors.forename: Motoya
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Hisaya
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Senji
authors.initials: S
authors.lastname: Shirasawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D000818:Animals; D002648:Child; D029721:Drosophila Proteins; D019334:Endothelin-3 / Q000235:genetics; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006627:Hirschsprung Disease / Q000150:complications / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics; D020182:Sleep Apnea, Central / Q000150:complications / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D019334:Endothelin-3; C495039:GDNF protein, human; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C489494:TLX3 protein, human; C487378:Tlx1 protein, mouse; C071250:TLX1 protein, human; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse