title: Mutational analysis of the RNX gene in congenital central hypoventilation syndrome.
abstract: Congenital central hypoventilation syndrome (CCHS) is a rare syndrome characterized by failure of autonomic respiratory control, often presenting with other dysfunctions of the autonomic nervous system. Segregation analysis suggested a complex model of inheritance with a major locus involved. Disruption of the Rnx gene, a member of the Hox11 family of homeobox genes, in embryonic stem cells produced mice showing a phenotype similar to CCHS. Based on this observation, we have carried out mutation screening of the RNX gene in a set of 13 patients affected with CCHS, 2 of whom showing association with Hirschsprung disease. Single-strand conformational polymorphism analysis and direct sequencing of the whole coding portion of the RNX gene and of 1,311 bp of 5' flanking region were performed. No sequence variant was identified, with the exception of a private nucleotide change at position -874 bp from the ATG codon in two siblings affected with isolated CCHS. A functional test, performed by using the luciferase gene reporter system, has not shown any significant difference in the activity of the promoter region carrying this latter nucleotide change with respect to the wild-type allele. We conclude that RNX, and presumably its expression, are not altered in our index cases of CCHS.
authors.affiliation: Laboratorio di Genetica Molecolare, Istituto G. Gaslini, Genova, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Matera
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bachetti
authors.forename: Roberta
authors.initials: R
authors.lastname: Cinti
authors.forename: Margherita
authors.initials: M
authors.lastname: Lerone
authors.forename: Luigi
authors.initials: L
authors.lastname: Gagliardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Morandi
authors.forename: Mario
authors.initials: M
authors.lastname: Motta
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ottonello
authors.forename: Raffaele
authors.initials: R
authors.lastname: Piumelli
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Schober
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020182:Sleep Apnea, Central / Q000151:congenital / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; C487378:Tlx1 protein, mouse; C071250:TLX1 protein, human; D004247:DNA; D008156:Luciferases