title: Molecular analysis of congenital central hypoventilation syndrome.
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.
authors.affiliation: Department of Pediatrics, Yamagata Univercity School of Medicine, 2-2-2 Iida-nishi, 990-9585 Yamagata, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Sasaki
authors.forename: Masayo
authors.initials: M
authors.lastname: Kanai
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kijima
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: Shinsuke
authors.initials: S
authors.lastname: Otaki
authors.forename: Takenobu
authors.initials: T
authors.lastname: Koizumi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kusuda
authors.forename: Youhei
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Tuchiya
authors.forename: Wakako
authors.initials: W
authors.lastname: Yamamoto
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D017668:Age of Onset; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D007223:Infant; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012121:Respiration, Artificial; D020182:Sleep Apnea, Central / Q000235:genetics*; D013577:Syndrome
chemical_list: C495039:GDNF protein, human; C494987:GFRA1 protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases