PDF(Pubmed)
Abstract：
About 5-10% of neurofibromatosis type 1 (NF1) patients exhibit large genomic germline deletions that remove the NF1 gene and its flanking regions. The most frequent NF1 large deletion is 1.4 Mb, resulting from homologous recombination between two low copy repeats. This \"type-1\" deletion is associated with a severe clinical phenotype in NF1 patients, with several phenotypic manifestations including learning disability, a much earlier development of cutaneous neurofibromas, an increased tumour risk, and cardiovascular malformations. NF1 adjacent co-deleted genes could act as modifier loci for the specific clinical manifestations observed in deleted NF1 patients. Furthermore, other genetic modifiers (such as CNVs) not located at the NF1 locus could also modulate the phenotype observed in patients with large deletions. In this study, we analysed 22 NF1 deletion patients by genome-wide array-CGH with the aim (1) to correlate deletion length to observed phenotypic features and their severity in NF1 deletion syndrome, and (2) to identify whether the deletion phenotype could also be modulated by copy number variations elsewhere in the genome. We then review the role of co-deleted genes in the 1.4 Mb interval of type-1 deletions, and their possible implication in the main clinical features observed in this high-risk group of NF1 patients.
摘要：
约5-10%的1型神经纤维瘤病(NF1)患者表现出去除NF1基因及其侧翼区的大的基因组种系缺失。最常见的NF1大删除是1.4Mb，由两个低拷贝重复之间的同源重组产生。这种“1型”缺失与NF1患者的严重临床表型有关，有几种表型表现，包括学习障碍，皮肤神经纤维瘤的早期发展，肿瘤风险增加，和心血管畸形.NF1相邻的共同缺失基因可以作为修饰基因座，用于在缺失的NF1患者中观察到的特定临床表现。此外，不位于NF1基因座的其他遗传修饰因子(如CNV)也可以调节在大缺失患者中观察到的表型。在这项研究中,我们通过全基因组阵列CGH分析了22名NF1缺失患者，目的是（1）将缺失长度与观察到的表型特征及其在NF1缺失综合征中的严重程度相关联，和(2)鉴定缺失表型是否也可以被基因组中其他地方的拷贝数变异所调节。然后，我们回顾了共同缺失的基因在1型缺失的1.4Mb间隔中的作用，以及它们在NF1高危患者组中观察到的主要临床特征中的可能含义。
