Kim Min Jeong, Cheon Chong Kun
Department of Pediatrics, Maryknoll Medical Center, Pusan, Korea.
Department of Pediatrics, Pusan National University School of Medicine, Yangsan, Korea.
Korean J Pediatr. 2014 Sep;57(9):410-5. doi: 10.3345/kjp.2014.57.9.410. Epub 2014 Sep 30.
Neurofibromatosis 1 (NF1) is an autosomal dominant condition caused by an NF1 gene mutation. NF1 is also a multisystem disorder that primarily affects the skin and nervous system. The goal of this study was to delineate the phenotypic characterization and assess the NF1 mutational spectrum in patients with NF1.
A total of 42 patients, 14 females and 28 males, were enrolled in this study. Clinical manifestations and results of the genetic study were retrospectively reviewed.
Age of the patients at the time of NF1 diagnosis was 15.8±14.6 years (range, 1-62 years). Twelve patients (28.6%) had a family history of NF1. Among the 42 patients, Café-au-lait spots were shown in 42 (100%), neurofibroma in 31 (73.8%), freckling in 22 (52.4%), and Lisch nodules in seven (16.7%). The most common abnormal finding in the brain was hamartoma (20%). Mental retardation was observed in five patients (11.9%), seizures in one patient (2.4%), and plexiform neurofibromas (PNFs) in four patients (9.5%). One patient with PNFs died due to a malignant peripheral nerve sheath tumor in the chest cavity. Genetic analysis of seven patients identified six single base substitutions (three missense and three nonsense) and one small deletion. Among these mutations, five (71.4%) were novel (two missense mutations: p.Leu1773Pro, p.His1170Leu; two nonsense mutations: p.Arg2517(), p.Cys2371(); one small deletion: p.Leu1944Phefs(*)6).
The clinical characteristics of 42 Korean patients with NF1 were extremely variable and the mutations of the NF1 gene were genetically heterogeneous with a high mutation-detection rate.
神经纤维瘤病1型（NF1）是一种由NF1基因突变引起的常染色体显性遗传病。NF1也是一种多系统疾病，主要影响皮肤和神经系统。本研究的目的是描述NF1患者的表型特征并评估其NF1突变谱。
本研究共纳入42例患者，其中女性14例，男性28例。对临床表现和基因研究结果进行回顾性分析。
NF1诊断时患者的年龄为15.8±14.6岁（范围1-62岁）。12例患者（28.6%）有NF1家族史。42例患者中，42例（100%）有咖啡斑，31例（73.8%）有神经纤维瘤，22例（52.4%）有雀斑，7例（16.7%）有Lisch结节。脑部最常见的异常发现是错构瘤（20%）。5例患者（11.9%）有智力障碍，1例患者（2.4%）有癫痫发作，4例患者（9.5%）有丛状神经纤维瘤（PNF）。1例PNF患者死于胸腔恶性外周神经鞘瘤。对7例患者的基因分析发现了6个单碱基替换（3个错义突变和3个无义突变）和1个小缺失。在这些突变中，5个（71.4%）是新发现的（2个错义突变：p.Leu1773Pro、p.His1170Leu；2个无义突变：p.Arg2517()、p.Cys2371()；1个小缺失：p.Leu1944Phefs(*)6）。
42例韩国NF1患者的临床特征差异极大，NF1基因的突变具有遗传异质性且突变检出率高。
