An estimated 5–11% of patients with neurofibromatosis type-1 (NF1) harbour large deletions encompassing the NF1 gene and flanking regions. These NF1 microdeletions are subclassified into type 1, 2, 3 and atypical deletions which are distinguishable from each other by their extent and by the number of genes included within the deletion regions as well as the frequency of mosaicism with normal cells. Most common are type-1 NF1 deletions which encompass 1.4-Mb and 14 protein-coding genes. Type-1 deletions are frequently associated with overgrowth, global developmental delay, cognitive disability and dysmorphic facial features which are uncommon in patients with intragenic pathogenic NF1 gene variants. Further, patients with type-1 NF1 deletions frequently exhibit high numbers of neurofibromas and have an increased risk of malignant peripheral nerve sheath tumours. Genes located within the type-1 NF1 microdeletion interval and co-deleted with NF1 are likely to act as modifiers responsible for the severe disease phenotype in patients with NF1 microdeletions, thereby causing the NF1 microdeletion syndrome. Genotype/phenotype correlations in patients with NF1 microdeletions of different lengths are important to identify such modifier genes. However, these correlations are critically dependent upon the accurate characterization of the deletions in terms of their extent. In this review, we outline the utility as well as the shortcomings of multiplex ligation-dependent probe amplification (MLPA) to classify the different types of NF1 microdeletion and indicate the importance of high-resolution microarray analysis for correct classification, a necessary precondition to identify those genes responsible for the NF1 microdeletion syndrome.

估计有 5-11% 的 1 型神经纤维瘤病 (NF1) 患者存在大量缺失，包括NF1基因和侧翼区域。这些NF1微缺失被细分为 1、2、3 型和非典型缺失，这些缺失可以通过它们的范围和缺失区域中包含的基因数量以及与正常细胞的嵌合频率来区分。最常见的是 1 型NF1缺失，包括 1.4-Mb 和 14 个蛋白质编码基因。1 型缺失通常与过度生长、整体发育迟缓、认知障碍和畸形面部特征相关，这在具有基因内致病性NF1基因变异的患者中并不常见。此外，1 型患者NF1缺失经常表现出大量神经纤维瘤，并增加恶性周围神经鞘瘤的风险。位于 1 型NF1微缺失区间内并与NF1共同缺失的基因可能充当NF1微缺失患者严重疾病表型的修饰因子，从而导致NF1微缺失综合征。NF1患者的基因型/表型相关性不同长度的微缺失对于鉴定此类修饰基因很重要。然而，这些相关性严重依赖于缺失程度的准确表征。在这篇综述中，我们概述了多重连接依赖探针扩增 (MLPA) 对不同类型NF1微缺失进行分类的效用和缺点，并指出高分辨率微阵列分析对正确分类的重要性，这是识别的必要先决条件那些负责NF1微缺失综合征的基因。