Clinical Analysis And Genetic Diagnosis Of A Child With Neurofibroma Type 1 Complicated With Juvenile Xanthogranuloma

Background Neurofibromatosis is a spectrum of diseases in which Neurofibromatosis type I（NF1）and Neurofibromatosis type II（NF2）and schwannomatosis（SWN）form the spectrum of Neurofibromatosis.NF1 also known as von Recklinghausen’s disease,is a syndrome of inherited tumor predisposition,associated with malformations of the nervous system and other organ systems and tumor growth regardless of gender or race,with a frequency of 1 in 2500 to 1 in 3500.NF1,as a very common clinical autosomal dominant genetic disease,is mainly characterized by cafe-au-lait macules（CALM）,freckle-like pigmented skin neurofibroma in the axillary or groin fold,and iris Lisch nodules,which are mainly due to NF1 Multisystem damage caused by abnormal gene mutations is difficult to diagnose in infants due to the lack of characteristic clinical manifestations,so genetic testing is extremely important for the diagnosis of NF1 children.Juvenile xanthogranuloma is a benign,self-limiting reactive proliferative nonLangerhans cell histiocytic disease with a statistically significant incidence of JXG of approximately 1 in every million children and approximately 5% to 10% of NF1 patients develop JXG At present,the relationship between JXG and NF1 is not completely clear,but several reports suggest that NF1 should be vigilant in children with multiple JXG In recent years,Panel targeted sequencing has been used to screen out pathogenic genes by targeting exon capture and large-scale parallel sequencing for disease-related genes under study.The advantages of rapid economy and accuracy make it a common method to study genetic diseases.Objective Panel targeted sequencing combined with first-generation Sanger sequencing was used to detect related dermatological genes of a patient with multiple coffee spot and xanthogranuloma as the main manifestations and their family,so as to make clinical diagnosis and explore the pathogenesis.To understand the relationship between NF1 gene and phenotype through literature,is convenient to judge the prognosis of patients,and for early diagnosis of patients Genetic counseling and prenatal diagnosis help.Method Clinical data and peripheral blood of the patient and her parents were collected,and the combined analysis method of Panel targeted sequencing and Sanger sequencing was used for mutation gene detection.Firstly,peripheral BLOOD DNA was extracted to construct DNA library,and Ion was used Torrent sequencing platform was used for sequencing,primers were designed according to the mutation sites obtained by Panel targeted sequencing,first-generation Sanger sequencing platform was used to verify the measured mutation sites,and Seq Man software and related biological software were used to analyze the sequencing resultsResults 1.The clinical manifestations of the proband were mainly multiple coffeecolored patches on the trunk and yellow papules on the scalp,while the skin CT of multiple yellow papules on the scalp showed foam cells,and the diagnosis of juvenile xanthogranuloma was clear.2.The Panel targeted sequencing found propositus NF1 gene 23 extra child missing a mutation happened,c.3094 delt: p.C ys1032 Alafs,Sanger sequencing,confirmed that the first certificate and his mother,the NF1 gene of 23 extra show 3094 th base thymine bases on the child missing,cause The substitution of cysteine for alanine at position 1032 of the amino acid coding sequence resulted in the eventual production of abnormal NF1 protein,resulting in the loss of its normal function,confirming the diagnosis of NF1,and this mutation site was reported for the first time.Conclusion Panel targeted sequencing combined with Sanger sequencing can quickly and economically detect the mutation sites of known pathogenic genes by pairing 1 A family of genetic testing,make the existing clinical phenotypes of patients has been clear about the clinical diagnosis,found a new gene mutations,enriched NF1 gene mutation spectrum,at the same time possible as early childhood patients with juvenile yellow granuloma early diagnosis on the basis of a reminder NF1 also consulting for the clinical disease treatment of NF1 diseases and provides a certain basis of prenatal diagnosis.