Neurofibromatosis type I（NF1） is a hereditary,autosomal dominant,neurocutaneous syndrome that is attributed to NF1 gene mutation.NF1 has been associated with scoliosis,macrocephaly,pseudoarthrosis,short stature,mental retardation,and malignancies.NF1-associated vasculopathy is an uncommon and easily-overlooked presentation.Examination of a Chinese family affected by NF1 combined with cerebral vessel stenosis and/ or abnormality suggested a possible relationship between NF1 and vessel stenosis.To determine which NF1 gene mutation is associated with vascular lesions,particularly cerebral vessel stenosis,we examined one rare family with combined cerebral vessel lesions or maldevelopment.Vascular lesions were detected using transcranial Doppler sonography and digital subtraction angiography in family members.Next,denaturing high-performance liquid chromatography and sequencing were used to screen for NF1 gene mutations.The results revealed a nonsense mutation,c.541C＆gt;T,in the NF1 gene.This mutation truncated the NF1 protein by 2659 aminoacid residues at the C-terminus and co-segregated with all of the patients,but was not present in unaffected individuals in the family.Exceptionally,three novel mutations were identified in unaffected family members,but these did not affect the product of the NF1 gene.Thus the nonsense mutation,c.541C＆gt;T,located in the NF1 gene could constitute one genetic factor for cerebral vessel lesions.
Ⅰ型神经纤维瘤病(neurofibromatosis type 1,NF1),也称Von Recklinghausen病,是一种常见的多系统遗传病,累及包括皮肤、中枢及周围神经系统、骨骼、脉管系统及内分泌系统等多个系统。其发病基因为Nf1,属于抑癌基因,定位于17q11.2,其编码的神经纤维瘤蛋白是Ras通路的重要抑制因子,调控多种细胞的增殖与分化。尽管血管病变较皮肤神经纤维瘤等典型症状少见,但会导致血管的狭窄、阻塞、动脉瘤等,甚至引起血管破裂,是导致NF1患者青少年人群过早病死的主要原因,严重影响NF1患者的预后。NF1相关血管病变发病机制十分复杂,包括血管生长因子分泌的增加、炎性细胞的参与等,近年来对其机制的深入研究也为其治疗带来新的突破。本文就NF1相关血管病变机制的研究进展进行综述。
