RGD Reference Report - Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. - Rat Genome Database

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Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome.

Authors: Amiel, J  Laudier, B  Attie-Bitach, T  Trang, H  De Pontual, L  Gener, B  Trochet, D  Etchevers, H  Ray, P  Simonneau, M  Vekemans, M  Munnich, A  Gaultier, C  Lyonnet, S 
Citation: Amiel J, etal., Nat Genet. 2003 Apr;33(4):459-61. Epub 2003 Mar 17.
RGD ID: 1599148
Pubmed: PMID:12640453   (View Abstract at PubMed)
DOI: DOI:10.1038/ng1130   (Journal Full-text)

Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a life-threatening disorder involving an impaired ventilatory response to hypercarbia and hypoxemia. This core phenotype is associated with lower-penetrance anomalies of the autonomic nervous system (ANS) including Hirschsprung disease and tumors of neural-crest derivatives such as ganglioneuromas and neuroblastomas. In mice, the development of ANS reflex circuits is dependent on the paired-like homeobox gene Phox2b. Thus, we regarded its human ortholog, PHOX2B, as a candidate gene in CCHS. We found heterozygous de novo mutations in PHOX2B in 18 of 29 individuals with CCHS. Most mutations consisted of 5-9 alanine expansions within a 20-residue polyalanine tract probably resulting from non-homologous recombination. We show that PHOX2B is expressed in both the central and the peripheral ANS during human embryonic development. Our data support an essential role of PHOX2B in the normal patterning of the autonomous ventilation system and, more generally, of the ANS in humans.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypoventilation  IAGP 1599148 RGD 
Hypoventilation  ISOPHOX2B (Homo sapiens)1599148; 1599148 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Phox2b  (paired-like homeobox 2b)

Genes (Mus musculus)
Phox2b  (paired-like homeobox 2b)

Genes (Homo sapiens)
PHOX2B  (paired like homeobox 2B)


Additional Information