Clinical Researches
Clinical phenotype and genetic analysis of neurofibromatosis type 1 caused by neurofibromatosis type 1 gene mutation
Mei Daoqi, Mei Shiyue, Chen Guohong, Wang Yuan, Wang Xiaona, Tang Zhihui, Chen Xiaoyi, Li Dongxiao, Zhang Yaodong
Published 2020-11-08
Cite as Chin J Neurol, 2020, 53(11): 910-917. DOI: 10.3760/cma.j.cn113694-20200723-00566
Abstract
ObjectiveTo investigate the clinical phenotype and summarize the genetic characteristics of children with neurofibromatosis type 1 (NF1) diagnosed by next-generation sequencing.
MethodsThe clinical data of 12 children with NF1 who were admitted to the Department of Neurology of the Children's Hospital Affiliated to Zhengzhou University from December 2017 to October 2019 were retrospectively analyzed. The next-generation sequencing method was used to sequence the NF1 gene of the probands and the mutations were verified by PCR-Sanger sequencing.
ResultsAmong the 12 children diagnosed with NF1 (male: female=11: 1), who aged from seven months to 11 years old, the main complaints were seizures and skin with café-au-lait spots. Five children were found with freckles in axillae, and two with cutaneous neurofibroma. Six cases had seizures, two children suffered spastic seizures, two with generalized tonic-clonic seizures, one with typical absence seizure, one with focal seizure, one case had severe headache and vomiting. Fortunately for the children with seizures, anti-epileptic drugs had a good prognosis. There were five mutation types detected in 12 cases, including one case of loss of overall heterozygosity in NF1 gene; three missense mutations: c.7867C>A (p.L2623I), c.7855C>A (p.L2619I) and c.7792C>A(p.L2598I); three frameshift mutations: c.3162delC(p.N1054Nfs*8), c.540dupA (p.Q181Tfs*20) and c.2027dupA(p.V679Pfs*21); three nonsense mutations: c.1467T>A(p.Y489X, 2351), c.1318C>T(p.R440X, 2400) and c.1411C>T(p.K471X, 2369); two splicing mutations: c.2326-2(IVS10)G>C and c.1186-1(IVS10)G>C. Nine children were found with spontaneous mutations, one case was inherited from the father, and two cases were inherited from the mother. c.7867C>A(p.L2623I), c.7855C>A(p.L2619I), c.3162delC(p.N1054Nfs*8), c.1411C>T(p.K471X, 2369), c.2326-2(IVS10)G>C, c.1186-1(IVS10)G>C were unreported mutations in literature.
ConclusionsNF1 is caused by NF1 gene mutation. The early clinical manifestations of children with NF1 defect presented with café-au-lait spots, and some suffered seizures. For patients with multiple café-au-lait spots and seizures in the clinic, genetic analysis should be performed as soon as possible to confirm the diagnosis.
Key words:
Neurofibromatosis type 1; NF1 gene; Café-au-lait spots; Epilepsy
Contributor Information
Mei Daoqi
Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450018, China
Mei Shiyue
Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Henan Engineering Research Center of Childhood Neurodevelopment, Zhengzhou 450018, China
Chen Guohong
Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450018, China
Wang Yuan
Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450018, China
Wang Xiaona
Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Henan Engineering Research Center of Childhood Neurodevelopment, Zhengzhou 450018, China
Tang Zhihui
Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450018, China
Chen Xiaoyi
Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450018, China
Li Dongxiao
Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Henan Engineering Research Center of Childhood Neurodevelopment, Zhengzhou 450018, China
Zhang Yaodong
Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Henan Engineering Research Center of Childhood Neurodevelopment, Zhengzhou 450018, China
