Douglas Jenny, Cilliers Deirdre, Coleman Kim, Tatton-Brown Katrina, Barker Karen, Bernhard Brigitte, Burn John, Huson Susan, Josifova Dragana, Lacombe Didier, Malik Mohsin, Mansour Sahar, Reid Evan, Cormier-Daire Valerie, Cole Trevor, Rahman Nazneen
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Nat Genet. 2007 Aug;39(8):963-5. doi: 10.1038/ng2083. Epub 2007 Jul 15.
17q11 microdeletions that encompass NF1 cause 5%-10% of cases of neurofibromatosis type 1, and individuals with microdeletions are typically taller than individuals with intragenic NF1 mutations, suggesting that deletion of a neighboring gene might promote human growth. We identified mutations in RNF135, which is within the NF1 microdeletion region, in six families characterized by overgrowth, learning disability, dysmorphic features and variable additional features. These data identify RNF135 as causative of a new overgrowth syndrome and demonstrate that RNF135 haploinsufficiency contributes to the phenotype of NF1 microdeletion cases.
包含NF1的17q11微缺失导致5%-10%的1型神经纤维瘤病病例，且微缺失个体通常比基因内NF1突变个体更高，这表明邻近基因的缺失可能促进人类生长。我们在六个以生长过度、学习障碍、畸形特征及各种其他特征为特点的家族中，鉴定出位于NF1微缺失区域内的RNF135基因发生了突变。这些数据确定RNF135是一种新的过度生长综合征病因，并证明RNF135单倍体不足导致了NF1微缺失病例的表型。
