Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Medical College of Soochow University, Suzhou, China.
Mol Genet Genomic Med. 2019 Sep;7(9):e904. doi: 10.1002/mgg3.904. Epub 2019 Jul 25.
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with equal sex incidence that is characterized by neurofibromas, café-au-lait macules, axillary freckling, optic pathway tumor, distinctive osseous lesion, and iris Lisch nodules. Inactivating variants in the NF1 gene have been identified to be correlated with NF1. This tumor suppressor gene is located at 17q11.2.
Ten affected NF1 probands and their available relatives from 10 unrelated Chinese families with neurofibromatosis type 1 were clinically studied. All of these probands mainly complained of osseous lesions. PCR was used to analyze and sequence the variants. We collected both laboratory and radiological information.
We detected five novel pathogenic variants including two de novo variants in these 10 families: one missense variant, p.Cys709Arg(c.2125T>C), in exon 18 and four frameshift variants: p.Leu1459Profs2(c.4436dupT) in exon 34; p.Lys99Argfs4(c.296delA) in exon 4; p.Leu762Cysfs2(c.2283delA) in exon 19; and p.Leu1522Ilefs53(c.4562_4563dupAT) in exon 34.
Novel pathogenic variants in the NF1 gene in these families correlated with the phenotype and genotype and explained the clinical manifestations of these patients. The results help us to understand the genetic basis of patients with neurofibromatosis type 1 in China. Our study expands the pathogenic variant spectrum of the NF1 gene and may be helpful in genetic counseling and prenatal genetic diagnosis.
神经纤维瘤病 1 型（NF1）是一种常染色体显性遗传病，男女发病率相等，其特征是神经纤维瘤、咖啡牛奶斑、腋窝雀斑、视路肿瘤、独特的骨骼病变和虹膜利什结节。已经发现 NF1 基因中的失活变异与 NF1 相关。这个肿瘤抑制基因位于 17q11.2。
对 10 个来自 10 个无关中国 NF1 家系的 NF1 先证者及其可利用亲属进行临床研究。所有这些先证者主要抱怨骨骼病变。使用 PCR 分析和测序变体。我们收集了实验室和影像学信息。
在这 10 个家庭中，我们检测到了 5 种新的致病性变异，包括 2 种从头变异：外显子 18 中的错义变异 p.Cys709Arg(c.2125T>C)和外显子 34 中的 4 种移码变异：p.Leu1459Profs2(c.4436dupT)；p.Lys99Argfs4(c.296delA)；p.Leu762Cysfs2(c.2283delA)；p.Leu1522Ilefs53(c.4562_4563dupAT)。
这些家系中 NF1 基因的新致病性变异与表型和基因型相关，并解释了这些患者的临床表现。结果有助于我们了解中国神经纤维瘤病 1 型患者的遗传基础。我们的研究扩展了 NF1 基因的致病性变异谱，可能有助于遗传咨询和产前遗传诊断。
