表型温和的1型神经纤维瘤病：5个家系基因突变分析

doi:10.35541/cjd.20201263

Abstract

Abstract: 【Abstract】 Objective To detect gene mutations in patients with mild phenotypes of neurofibromatosis type 1 （NF1）. Methods From June 2017 to June 2020, 5 probands with mild phenotypes of NF1 only involving lesions and their family members were collected from Department of Dermatology, Fengxian Institute of Dermatosis Prevention and Treatment in Shanghai. Pedigree investigation was performed to evaluate the clinical phenotypes of NF1. The second-generation targeted gene sequencing combined with Sanger sequencing was performed to detect and verify pathogenic mutations. Results All the 5 probands only presented with skin lesions, including café-au-lait spots, freckles, neurofibromas, without other systemic involvement. A total of 5 mutations were identified in different exons of the NF1 gene in the 5 families, including 1 large-fragment deletion mutation （hg38: chr17:31327199-31335928 del 8 730 bp）, 1 splicing mutation （C.7970+1G>T）, 1 insertion mutation （C.3011_3012insTATG, p.N1004fs*）, 1 deletion mutation （C.1754_1757delTAAC, p.T586Vfs*18）, and 1 nonsense mutation （c.C503G, p.S168X）, and the first 3 above mentioned mutations were unreported novel mutations. Conclusion Five mutations were identified in the 5 families with mild phenotypes of NF1, including 3 novel mutations, which expand the mutational spectrum of NF1.

Key words: Neurofibromatosis 1, DNA mutational analysis, Phenotype

Zhu Ying, Guo Yunyi, Zhang Danlu, Guo Birong, Sun Zhonghui. Mutation analysis in 5 families with mild phenotypes of neurofibromatosis type 1[J]. Chinese Journal of Dermatology, 2022, 55(6): 519-522.doi:10.35541/cjd.20201263

References ［19］

［1］	Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neuro⁃fibromatosis 1 and neurofibromatosis 2［J］. JAMA, 1997,278（1）:51⁃57.
［2］	Zhang J, Tong H, Fu X, et al. Molecular Characterization of NF1 and Neurofibromatosis Type 1 Genotype⁃Phenotype Correlations in a Chinese Population［J］. Sci Rep, 2015,5:11291. doi: 10. 1038/srep11291.
［3］	Mautner VF, Kluwe L, Friedrich RE, et al. Clinical characterisation of 29 neurofibromatosis type⁃1 patients with molecularly ascertained 1.4 Mb type⁃1 NF1 deletions［J］. J Med Genet, 2010,47（9）:623⁃630. doi: 10.1136/jmg.2009.075937.
［4］	孙忠辉, 李明, 郭韫懿, 等. 基因检测诊断仅有咖啡色斑表现的儿童Ⅰ型神经纤维瘤病一例［J］. 中华皮肤科杂志, 2013,46（7）:511⁃512. doi: 10.3760/cma.j.issn.0412⁃4030.2013.07.019.
［5］	Nemethova M, Bolcekova A, Ilencikova D, et al. Thirty⁃nine novel neurofibromatosis 1 （NF1） gene mutations identified in Slovak patients［J］. Ann Hum Genet, 2013,77（5）:364⁃379. doi: 10.1111/ahg.12026.
［6］	倪成. 遗传性角化性皮肤病基因型-表型关系研究［D］. 上海: 上海交通大学, 2016.
［7］	Mao B, Chen S, Chen X, et al. Clinical characteristics and spectrum of NF1 mutations in 12 unrelated Chinese families with neurofibromatosis type 1［J］. BMC Med Genet, 2018,19（1）:101. doi: 10.1186/s12881⁃018⁃0615⁃8.
［8］	Corsello G, Antona V, Serra G, et al. Clinical and molecular characterization of 112 single⁃center patients with Neurofibromatosis type 1［J］. Ital J Pediatr, 2018,44（1）:45. doi: 10.1186/s13052⁃018⁃0483⁃z.
［9］	Wimmer K, Yao S, Claes K, et al. Spectrum of single⁃ and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients［J］. Genes Chromosomes Cancer, 2006,45（3）:265⁃276. doi: 10.1002/gcc.20289.
［10］	Zhu L, Zhang Y, Tong H, et al. Clinical and molecular characterization of NF1 patients: single⁃center experience of 32 patients from China［J］. Medicine （Baltimore）, 2016,95（10）:e3043. doi: 10.1097/MD.0000000000003043.
［11］	Orzan F, Stroppi M, Venturin M, et al. Breakpoint characterization of a novel NF1 multiexonic deletion: a case showing expression of the mutated allele［J］. Neurogenetics, 2008,9（2）:95⁃100. doi: 10.1007/s10048⁃007⁃0115⁃z.
［12］	Jang MA, Kim YE, Kim SK, et al. Identification and characterization of NF1 splicing mutations in Korean patients with neurofibromatosis type 1［J］. J Hum Genet, 2016,61（8）:705⁃709. doi: 10.1038/jhg.2016.33.
［13］	Ars E, Serra E, García J, et al. Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1［J］. Hum Mol Genet, 2000,9（2）:237⁃247. doi: 10.1093/hmg/9.2.237.
［14］	Faravelli F, Upadhyaya M, Osborn M, et al. Unusual clustering of brain tumours in a family with NF1 and variable expression of cutaneous features［J］. J Med Genet, 1999,36（12）:893⁃896.
［15］	Trevisson E, Morbidoni V, Forzan M, et al. The Arg1038Gly missense variant in the NF1 gene causes a mild phenotype without neurofibromas［J］. Mol Genet Genomic Med, 2019,7（5）:e616. doi: 10.1002/mgg3.616.
［16］	Koczkowska M, Callens T, Gomes A, et al. Expanding the clinical phenotype of individuals with a 3⁃bp in⁃frame deletion of the NF1 gene （c.2970_2972del）: an update of genotype⁃phenotype correlation［J］. Genet Med, 2019,21（4）:867⁃876. doi: 10.1038/s41436⁃018⁃0269⁃0.
［17］	Rojnueangnit K, Xie J, Gomes A, et al. High incidence of noonan syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p.arg1809: genotype⁃phenotype correlation［J］. Hum Mutat, 2015,36（11）:1052⁃1063. doi: 10.1002/humu.22832.
［18］	Guo Y, Zhu Y, Zhang D, et al. Typical Chinese pedigree of autosomal dominant genetic disease: neurofibromatosis type 1 with a novel frame⁃shift mutation［J］. J Dermatol, 2017,44（8）:e188⁃e189. doi: 10.1111/1346⁃8138.13899.
［19］	Griffiths S, Thompson P, Frayling I, et al. Molecular diagnosis of neurofibromatosis type 1: 2 years experience［J］. Fam Cancer, 2007, 6（1）:21⁃34. doi: 10.1007/s10689⁃006⁃9001⁃3.

[1]	Chen Xinqi, Zhao Juan, Wang Peng, Li Tingting, Yu Shirong, Kang Xiaojing. Association between clinicopathological characteristics and gene mutations in 94 cases of cutaneous melanoma [J]. Chinese Journal of Dermatology, 2022, 55(5): 395-400.
[2]	Chen Yuping, Zheng Hailin, Zhang Zhifeng, Mei Huan, Liu Weida, Liu Musang. Retrospective analysis of 201 clinical isolates of Aspergillus fumigatus from a hospital in Nanjing: clinical characteristics of infected patients and azole resistance [J]. Chinese Journal of Dermatology, 2022, 55(4): 316-320.
[3]	Liu Chenmei, Chen Hongyu, Chen Pingjiao, Zeng Kang, Li Changxing. Identification of pathogenic genes in a family with oculocutaneous albinism [J]. Chinese Journal of Dermatology, 2022, 0(2): 20210393-e20210393.
[4]	Lian Jia, Qin Bei, Li Qinfeng. A novel mutation in the ALOX12B gene in hereditary ichthyosis: pedigree analysis for a female collodion baby [J]. Chinese Journal of Dermatology, 2022, 0(2): 20201135-e20201135.
[5]	Li Bo, Wen Guangdong, Yu Cong, Zhang Jianzhong, Zhou Cheng. Gene mutation analysis of a family with familial generalized lentiginosis [J]. Chinese Journal of Dermatology, 2022, 55(2): 146-149.
[6]	Wang Wenzhu, Wang Baoxi, He Yanyan, Xu Haoxiang. Clinical phenotypes and genotypes of hidradenitis suppurativa/acne inversa [J]. Chinese Journal of Dermatology, 2022, 0(1): 20210252-e20210252.
[7]	Yang Zhou, Xu Zhe, Wang Zhaoyang, Chen Yunliu, Ma Lin. TP63 gene mutation analysis in a case of ankyloblepharon-ectodermal dysplasia-clefting syndrome [J]. Chinese Journal of Dermatology, 2021, 54(网络首发): 20201051-e20201051.
[8]	Chen Yingdan, Huang Hui, Luo Shuaihantian, Li Yaping, Shi Xiaoliu, Zhang Guiying. A case of atypical late-onset Netherton syndrome without bamboo hair [J]. Chinese Journal of Dermatology, 2021, 54(8): 716-718.
[9]	He Tianrong, Liu Yunqiang, Yang Yuan. A study on pathogenicity of TGM1 gene mutations in a collodion baby [J]. Chinese Journal of Dermatology, 2021, 54(8): 712-715.
[10]	Liu Yihe, Chen Zhiming, Yang Yong. Chanarin-Dorfman syndrome: the first case reported in China [J]. Chinese Journal of Dermatology, 2021, 54(8): 673-676.
[11]	Wu Yali, Mei Juan, Zhao Lingxia, Yin Wei. A de novo mutation in the PORCN gene in a newborn with Goltz syndrome [J]. Chinese Journal of Dermatology, 2021, 54(6): 514-517.
[12]	Wang Xiaopo, Chen Zhiming, Yang Yong, Sun Jianfang . A family of severe epidermolysis bullosa simplex caused by a de novo mutation in the KRT5 gene [J]. Chinese Journal of Dermatology, 2021, 54(3): 229-231.
[13]	Zhou Jie, Song Zhiqiang. Clinical phenotypes and endophenotypes of atopic dermatitis [J]. Chinese Journal of Dermatology, 2021, 54(3): 259-263.
[14]	Qin Bei, Li Qinfeng, Lian Jia. An infant with lamellar ichthyosis induced by CYP4F22 gene mutations [J]. Chinese Journal of Dermatology, 2021, 54(12): 1096-1098.
[15]	Liu Liqin, Wang Jinyan, Jiao Ting, Zhang Li, Han Changyuan, Ye Yingyi. Mutation analysis of the PTPN11 gene in a pedigree with LEOPARD syndrome [J]. Chinese Journal of Dermatology, 2021, 54(11): 998-1000.

Mutation analysis in 5 families with mild phenotypes of neurofibromatosis type 1

PDF

PDF (Mobile)

Knowledge

Abstract

Cite this article

share this article

References ［19］

Related Articles 15

Metrics

Comments

Recommended 10