Moncla Anne, Missirian Chantal, Cacciagli Pierre, Balzamo Eve, Legeai-Mallet Laurence, Jouve Jean-Luc, Chabrol Brigitte, Le Merrer Martine, Plessis Ghislaine, Villard Laurent, Philip Nicole
Assistance Publique-Hôpitaux de Marseille, Hôpital d'Enfants de La Timone, Departement de Génétique, Marseille, France.
Hum Mutat. 2007 Dec;28(12):1183-8. doi: 10.1002/humu.20611.
Overexpression of the C-type natriuretic peptide, encoded by the NPPC gene in 2q37.1, was recently reported in a patient presenting an overgrowth phenotype and a balanced t(2;7)(q37.1;q21.3) translocation. We present clinical, cytogenetic, and molecular data from two additional patients carrying balanced translocations involving the same 2q37.1 chromosome band and chromosomes 8 and 13, respectively. The clinical phenotype of these patients is very similar to the first patient described. In addition to the overgrowth syndrome, there is evidence of generalized cartilage dysplasia. In these two new cases, we found overexpression of NPPC, confirming that this unusual overgrowth phenotype in humans is due to the overexpression of this gene. The involvement of three different chromosomes and a cluster of breakpoints around the NPPC gene suggests that the overexpression of this gene in translocation patients could be due to its separation from a negative regulatory element located on chromosome 2, which would constitute a previously undescribed mutational mechanism.
最近有报道称，一名表现出过度生长表型且存在平衡的t(2;7)(q37.1;q21.3)易位的患者中，位于2q37.1的NPPC基因编码的C型利钠肽出现过表达。我们展示了另外两名患者的临床、细胞遗传学和分子数据，这两名患者分别携带涉及相同的2q37.1染色体带以及8号和13号染色体的平衡易位。这些患者的临床表型与首例报道患者非常相似。除过度生长综合征外，还有全身软骨发育异常的证据。在这两例新病例中，我们发现NPPC过表达，证实人类这种不寻常的过度生长表型是由于该基因的过表达所致。三条不同染色体的参与以及NPPC基因周围的一个断点簇表明，易位患者中该基因的过表达可能是由于其与位于2号染色体上的一个负调控元件分离，这将构成一种此前未描述过的突变机制。
