Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Napoli, Italy.
Departement of Women's and Children's Health and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138 Napoli, Italy.
Genes (Basel). 2019 Jul 31;10(8):580. doi: 10.3390/genes10080580.
Pigmentary manifestations can represent an early clinical sign in children affected by Neurofibromatosis type 1 (NF1), Legius syndrome, and other neurocutaneous disorders. The differential molecular diagnosis of these pathologies is a challenge that can now be met by combining next generation sequencing of target genes with concurrent second-level tests, such as multiplex ligation-dependent probe amplification and RNA analysis. We clinically and genetically investigated 281 patients, almost all pediatric cases, presenting with either NF1 ( = 150), only pigmentary features (café au lait macules with or without freckling; ( = 95), or clinical suspicion of other RASopathies or neurocutaneous disorders ( = 36). The causative variant was identified in 239 out of the 281 patients analyzed (85.1%), while 42 patients remained undiagnosed (14.9%). The and genes were mutated in 73.3% and 2.8% of cases, respectively. The remaining 8.9% carried mutations in different genes associated with other disorders. We achieved a molecular diagnosis in 69.5% of cases with only pigmentary manifestations, allowing a more appropriate clinical management of these patients. Our findings, together with the increasing availability and sharing of clinical and genetic data, will help to identify further novel genotype-phenotype associations that may have a positive impact on patient follow-up.
色素沉着表现可能是 1 型神经纤维瘤病（NF1）、莱格氏综合征和其他神经皮肤疾病患儿的早期临床征象。这些病变的差异分子诊断是一个挑战，现在可以通过将靶向基因的下一代测序与同时进行的二级测试（如多重连接依赖性探针扩增和 RNA 分析）相结合来实现。我们对 281 名患者进行了临床和基因研究，几乎所有患者均为儿科病例，表现为 NF1（=150）、仅色素沉着特征（咖啡牛奶斑伴或不伴雀斑；=95）或其他 RAS 病或神经皮肤疾病的临床可疑症状（=36）。在分析的 281 名患者中，有 239 名（85.1%）确定了致病变异，而 42 名患者仍未确诊（14.9%）。和 基因分别在 73.3%和 2.8%的病例中发生突变。其余 8.9%的患者携带与其他疾病相关的不同基因的突变。我们在仅表现出色素沉着的病例中实现了 69.5%的分子诊断，从而能够更好地管理这些患者。我们的发现，以及临床和遗传数据的日益普及和共享，将有助于确定进一步的新的基因型-表型关联，这可能对患者的随访产生积极影响。
