Trochet Delphine, Bourdeaut Franck, Janoueix-Lerosey Isabelle, Deville Anne, de Pontual Loïc, Schleiermacher Gudrun, Coze Carole, Philip Nicole, Frébourg Thierry, Munnich Arnold, Lyonnet Stanislas, Delattre Olivier, Amiel Jeanne
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, and Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
Am J Hum Genet. 2004 Apr;74(4):761-4. doi: 10.1086/383253. Epub 2004 Mar 11.
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.
神经母细胞瘤（NB）是一种常见的儿科肿瘤，已知其存在复发性体细胞重排。基于罕见的家族病例以及NB与其他神经嵴衍生细胞的遗传性先天性畸形（即先天性巨结肠病（HSCR）和/或先天性中枢性低通气综合征（CCHS））的关联，推测可能存在易感基因的种系突变。我们最近鉴定出配对样同源盒2B（PHOX2B）基因是孤立性和综合征性CCHS的主要致病基因，这促使我们将其视为NB的候选基因。在此，我们报告了一例NB家族病例和一名患有HSCR-NB关联患者中PHOX2B的种系突变。因此，PHOX2B是第一个种系突变易导致NB的基因。
