PHOX2B

Last updated

PHOX2B
Identifiers
Aliases PHOX2B , NBLST2, NBPhox, PMX2B, paired like homeobox 2b, CCHS
External IDs OMIM: 603851; MGI: 1100882; HomoloGene: 68371; GeneCards: PHOX2B; OMA:PHOX2B - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003924

NM_008888

RefSeq (protein)

NP_003915

NP_032914

Location (UCSC) Chr 4: 41.74 – 41.75 Mb Chr 5: 67.25 – 67.26 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Paired-like homeobox 2b (PHOX2B), also known as neuroblastoma Phox (NBPhox), is a protein that in humans is encoded by the PHOX2B gene located on chromosome 4. [5]

Contents

It codes for a homeodomain transcription factor. It is expressed exclusively in the nervous system, in most neurons that control the viscera (cardiovascular, digestive and respiratory systems). It is also required for their differentiation.

Immunohistochemistry

Essential for the differentiation and survival of sympathetic neurons and chromaffin cells, the transcription factor PHOX2B is highly specific for the peripheral autonomic nervous system. Neuroblasts are derived from sympathoadrenal lineage neural crest cells and therefore require and constitutively express PHOX2B. PHOX2B immunohistochemical staining, as a marker of neural crest derivation, has been shown to be sensitive and specific for undifferentiated neuroblastoma, enabling identification where other markers fail to recognize neuroblastoma among various different small round blue cell tumors of childhood. [6] [7] [8] [9]

The diagnostic utility of PHOX2B staining extends to later stages of differentiation. Its strength and specificity can detect the small foci of neuroblastic tumors metastatic to the bone marrow, an identification critical for determining disease staging. PHOX2B staining also overcomes frequent obstacles to neuroblastoma detection in post-treatment samples, which frequently exhibit dense fibrosis, prominent inflammatory infiltrates, and/or diffuse calcification. [10]

Pathology

Mutations in human PHOX2B cause a rare disease of the visceral nervous system (dysautonomia): congenital central hypoventilation syndrome (associated with respiratory arrests during sleep and, occasionally, wakefulness), Hirschsprung's disease (partial agenesis of the enteric nervous system), ROHHAD, and tumours of the sympathetic ganglia. In most people, Exon 3 of the gene contains a sequence of 20 polyalanine repeats. An increase in the number of repeats is associated with congenital central hypoventilation syndrome. There may also be other pathogenic mutations further along the gene.

Research into Phox2B

Organisations involved in researching Phox2B include those concerned with Congenitial Central Hypoventilation Syndrome. These include Keep Me Breathing [11] based in the UK and The CCHS Network based in the USA. The CCHS Network held a scientific conference in September 2023, which covered significant research into Phox2B and CCHS with Keep Me Breathing presenting, too. [12]

Related Research Articles

<span class="mw-page-title-main">Hirschsprung's disease</span> Medical condition

Hirschsprung's disease is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Most children develop signs and symptoms shortly after birth. However, others may be diagnosed later in infancy or early childhood. About half of all children with Hirschsprung's disease are diagnosed in the first year of life. Complications may include enterocolitis, megacolon, bowel obstruction and intestinal perforation.

<span class="mw-page-title-main">Central hypoventilation syndrome</span> Medical condition

Central hypoventilation syndrome (CHS) is a sleep-related breathing disorder that causes ineffective breathing, apnea, or respiratory arrest during sleep. CHS can either be congenital (CCHS) or acquired (ACHS) later in life. The condition can be fatal if untreated. CCHS was once known as Ondine's curse.

<span class="mw-page-title-main">Neuroblastoma</span> Genetically inherited cancer of certain nerve tissues

Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin.

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<span class="mw-page-title-main">PAX3</span> Paired box gene 3

The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.

<span class="mw-page-title-main">TCF4</span> Protein-coding gene in the species Homo sapiens

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LIM homeobox transcription factor 1-beta, also known as LMX1B, is a protein which in humans is encoded by the LMX1B gene.

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<span class="mw-page-title-main">GATA3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Endothelin 3</span> Protein-coding gene in the species Homo sapiens

Endothelin-3 is a protein that in humans is encoded by the EDN3 gene.

<span class="mw-page-title-main">ASCL1</span> Protein-coding gene in humans

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<span class="mw-page-title-main">CEP290</span> Protein-coding gene in the species Homo sapiens

Centrosomal protein of 290 kDa is a protein that in humans is encoded by the CEP290 gene. CEP290 is located on the Q arm of chromosome 12.

<span class="mw-page-title-main">TLX3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">ROHHAD</span> Medical condition

Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare condition whose etiology is currently unknown. ROHHAD mainly affects the endocrine system and autonomic nervous system, but patients can exhibit a variety of signs. Patients present with both alveolar hypoventilation along with hypothalamic dysfunction, which distinguishes ROHHAD from congenital central hypoventilation syndrome (CCHS). ROHHAD is a rare disease, with only 100 reported cases worldwide thus far.

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<span class="mw-page-title-main">Hereditary leiomyomatosis and renal cell cancer syndrome</span> Medical condition

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) or Reed's syndrome is rare autosomal dominant disorder associated with benign smooth muscle tumors and an increased risk of renal cell carcinoma. It is characterised by multiple cutaneous leiomyomas and, in women, uterine leiomyomas. It predisposes individuals to renal cell cancer, an association denominated hereditary leiomyomatosis and renal cell cancer. It is also associated with increased risk of uterine leiomyosarcoma. The syndrome is caused by a mutation in the fumarate hydratase gene, which leads to an accumulation of fumarate. The inheritance pattern is autosomal dominant and screening can typically begin in childhood.

Stanislas Lyonnet is a French geneticist. As of 2012 he was Professor of genetics at Paris Descartes University, and a clinical geneticist in the Department of Medical Genetics at the Hôpital Necker - Enfants Malades. His research is aimed at isolating the genes that cause congenital malformation and birth defects.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000109132 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000012520 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: paired-like homeobox 2b".
  6. Bielle F, Fréneaux P, Jeanne-Pasquier C, Maran-Gonzalez A, Rousseau A, Lamant L, et al. (August 2012). "PHOX2B immunolabeling: a novel tool for the diagnosis of undifferentiated neuroblastomas among childhood small round blue-cell tumors". The American Journal of Surgical Pathology. 36 (8): 1141–1149. doi:10.1097/PAS.0b013e31825a6895. PMID   22790854. S2CID   25924210.
  7. Hata JL, Correa H, Krishnan C, Esbenshade AJ, Black JO, Chung DH, et al. (April 2015). "Diagnostic utility of PHOX2B in primary and treated neuroblastoma and in neuroblastoma metastatic to the bone marrow". Archives of Pathology & Laboratory Medicine. 139 (4): 543–546. doi: 10.5858/arpa.2014-0255-OA . PMID   25822764.
  8. Hung YP, Lee JP, Bellizzi AM, Hornick JL (November 2017). "PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours". Histopathology. 71 (5): 786–794. doi:10.1111/his.13288. PMID   28640941. S2CID   19123236.
  9. Warren M, Matsuno R, Tran H, Shimada H (March 2018). "Utility of Phox2b immunohistochemical stain in neural crest tumours and non-neural crest tumours in paediatric patients". Histopathology. 72 (4): 685–696. doi:10.1111/his.13412. PMID   28986989. S2CID   3302863.
  10. Hata et al. (2015).
  11. "CCHS for Professionals – Keep Me Breathing" . Retrieved 2024-08-09.
  12. "2023 CCHS Science Conference". CCHS Network. Retrieved 2024-08-09.

Further reading