Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma - PubMed (original) (raw)

doi: 10.1086/383253. Epub 2004 Mar 11.

Franck Bourdeaut, Isabelle Janoueix-Lerosey, Anne Deville, Loïc de Pontual, Gudrun Schleiermacher, Carole Coze, Nicole Philip, Thierry Frébourg, Arnold Munnich, Stanislas Lyonnet, Olivier Delattre, Jeanne Amiel

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Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma

Delphine Trochet et al. Am J Hum Genet. 2004 Apr.

Abstract

Neuroblastoma (NB) is a frequent pediatric tumor for which recurrent somatic rearrangements are known. Germline mutations of predisposing gene(s) are suspected on the basis of rare familial cases and the association of NB with other genetically determined congenital malformations of neural crest-derived cells--namely, Hirschsprung disease (HSCR) and/or congenital central hypoventilation syndrome (CCHS). We recently identified the paired-like homeobox 2B (PHOX2B) gene as the major disease-causing gene in isolated and syndromic CCHS, which prompted us to regard it as a candidate gene in NB. Here, we report on germline mutations of PHOX2B in both a familial case of NB and a patient with the HSCR-NB association. PHOX2B, therefore, stands as the first gene for which germline mutations predispose to NB.

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Figure 1

Figure 1

PHOX2B mutations in familial and syndromic neuroblastoma. A, Pedigree of patients 1 and 2. B, Genomic organization of the PHOX2B protein. The homeobox domain and the 9- and 20-residue polyalanine tracts are indicated by blue and green boxes, respectively. C, DNA sequence electrophoregrams of exon 2 of the PHOX2B gene, showing missense heterozygous mutations in the homeobox. Wild-type (WT) (top) and mutant (bottom) sequences are indicated.

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References

Electronic-Database Information

    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for NB, HSCR, Ondine's curse, and PHOX2B)

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