PHOX2B

Pathology

 germline mutations in congenital central hypoventilation syndrome (polyalanine expansion and frameshift mutations)(MIM.209880) with or without neuroblastoma (15657873)
 germline mutations in short-segment Hirschsprung disease
 germline mutations in familial neuroblastoma

• PHOX2B-associated neuroblastoma

PHOX2B has been identified as a sensitive and specific minimal residual disease (MRD) marker; however, its expression varies between tumors. (19460840)

Immunochemistry

 PHOX2B Immunolabeling is a Novel Tool for the Diagnosis of Undifferentiated Neuroblastomas Among Childhood Small Round Blue-cell Tumors. (22790854)

• PHOX2B is expressed in all undifferentiated neuroblastomas tested and in no other small round blue-cell tumors.
• PHOX2B immunohistochemical analysis improves the diagnosis of undifferentiated neuroblastoma with high specificity and sensitivity.

Lignads

 The E3 ubiquitin ligase TRIM11 mediates the degradation of congenital central hypoventilation syndrome-associated polyalanine-expanded PHOX2B. (22307522)

See also

 polyalanine repeat expansions
 Hirschsprung disease genes

RET

GDNF

NRTN

SOX10

EDNRB

EDN3

ECE1

ZFHX1B

PHOX2B

TCF4

References

 PHOX2B Immunolabeling: A Novel Tool for the Diagnosis of Undifferentiated Neuroblastomas Among Childhood Small Round Blue-cell Tumors. Bielle F, Fréneaux P, Jeanne-Pasquier C, Maran-Gonzalez A, Rousseau A, Lamant L, Paris R, Pierron G, Nicolas AV, Sastre-Garau X, Delattre O, Bourdeaut F, Peuchmaur M. Am J Surg Pathol. 2012 Aug;36(8):1141-1149. PMID: 22790854

 Comparison of PHOX2B testing methods in the diagnosis of congenital central hypoventilation syndrome and mosaic carriers. Jennings LJ, Yu M, Zhou L, Rand CM, Berry-Kravis EM, Weese-Mayer DE. Diagn Mol Pathol. 2010 Dec;19(4):224-31. PMID: 21051998

 Detecting minimal residual disease in neuroblastoma: the superiority of a panel of real-time quantitative PCR markers. Stutterheim J, Gerritsen A, Zappeij-Kannegieter L, Yalcin B, Dee R, van Noesel MM, Berthold F, Versteeg R, Caron HN, van der Schoot CE, Tytgat GA. Clin Chem. 2009 Jul;55(7):1316-26. PMID: 19460840

 Trochet D, de Pontual L, Estêvao MH, Mathieu Y, Munnich A, Feingold J, Goridis C, Lyonnet S, Amiel J. Homozygous mutation of the PHOX2B gene in congenital central hypoventilation syndrome (Ondine’s Curse). Hum Mutat. 2008 May;29(5):770. PMID: 18407552

 Trochet D, de Pontual L, Straus C, Gozal D, Trang H, Landrieu P, Munnich A, Lyonnet S, Gaultier C, Amiel J. PHOX2B germline and somatic mutations in late-onset central hypoventilation syndrome. Am J Respir Crit Care Med. 2008 Apr 15;177(8):906-11. PMID: 18079495

 de Pontual L, Trochet D, Bourdeaut F, Thomas S, Etchevers H, Chompret A, Minard V, Valteau D, Brugieres L, Munnich A, Delattre O, Lyonnet S, Janoueix-Lerosey I, Amiel J. Methylation-associated PHOX2B gene silencing is a rare event in human neuroblastoma. Eur J Cancer. 2007 Nov;43(16):2366-72. PMID: 17765533

 Amiel, J.; Laudier, B.; Attie-Bitach, T.; Trang, H.; de Pontual, L.; Gener, B.; Trochet, D.; Etchevers, H.; Ray, P.; Simmoneau, M.; Vekemans, M.; Munnich, A.; Gaultier, C.; Lyonnet, S. : Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nature Genet. 33: 459-460, 2003. PubMed ID : 12640453