Sudden death in young people

Gene: PHOX2B

Green List (high evidence)

PHOX2B (paired like homeobox 2b)
EnsemblGeneIds (GRCh38): ENSG00000109132
EnsemblGeneIds (GRCh37): ENSG00000109132
OMIM: 603851, Gene2Phenotype
PHOX2B is in 11 panels

3 reviews

Ellen Thomas (Genomics England Curator)

Comment on list classification: Poor evidence of association between repeat length and SIDs in case-control studies; however, good evidence that this gene causes central hypoventilation, which frequently affects babies and can lead to death, so this should be included. Some small indels as well as the polyalanine expansion.
Created: 19 Dec 2016, 3:55 p.m.

Alice Gardham (Genomics England)

Comment on mode of pathogenicity: Nucleotide repeat expansion. Tagged 5.12.16 by Alice Gardham
Created: 5 Dec 2016, 2:40 p.m.

Rebecca Foulger (Genomics England curator)

The role of PHOX2B in sudden death is disputed: mutations in PHOX2B are a common cause of congenital central hypoventilation syndrome (CCHS), which is considered one of the compromised conditions in sudden infant death syndrome (SIDS). In an association study, PMID:24442913 (2014) report that length variation of the polyalanine repeat in exon 3 of the PHOX2B gene is associated with USID/SIDS in the Dutch population. However, an earlier paper PMID:15185974 (Kijima et al., 2004) report that SIDS is NOT associated with mutation of the PHOX2B gene.
Created: 29 Nov 2016, 9:56 a.m.

Mode of pathogenicity
Other

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Literature
  • Other
Phenotypes
  • sudden infant death syndrome
  • unclassified sudden infant death
  • USID
  • Congenital Central Hypoventilation Syndrome
  • CCHS
  • Central hypoventilation syndrome, congenital, with or without Hirschsprung disease, 209880
Tags
nucleotide-repeat-expansion
OMIM
603851
Clinvar variants
Variants in PHOX2B
Penetrance
Complete
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

19 Dec 2016, Gel status: 4

panel promoted to version 1

Ellen Thomas (Genomics England Curator)

This panel contains genes which aren't arrhythmic or metabolic causes of sudden death with normal post mortem.

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

5 Dec 2016, Gel status: 2

Set mode of pathogenicity

Alice Gardham (Genomics England)

Mode of pathogenicity for PHOX2B was changed to Other - please provide details in the comments

29 Nov 2016, Gel status: 2

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

PHOX2B was added to Sudden death in young peoplepanel. Source: Radboud University Medical Center, Nijmegen Model of inheritance for gene PHOX2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

29 Nov 2016, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

PHOX2B was added to Sudden death in young peoplepanel. Source: Emory Genetics Laboratory

29 Nov 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

PHOX2B was added to Sudden death in young peoplepanel. Source: Literature

29 Nov 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

PHOX2B was added to Sudden death in young peoplepanel. Sources: Other

29 Nov 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

PHOX2B was created by rfoulger