Clinical Analysis And Gene Mutation Of Type 1 Neurofibroma With Skull Defect

Objective:Neurofibromatosis type 1(NF1)is one of autosomal dominant genetic diseases caused by tumor suppressor gene mutation.The non neoplastic symptoms of this disease include mental deficiency,bone deformation,etc.in this study,a patient with sporadic neurofibromatosis type 1 complicated with skull defect was studied for clinical manifestations,gene sequencing analysis and bioinformatics prediction,Identify the possible pathogenic genes,so as to enrich the mutation spectrum of NF1 gene in Chinese population.To compare the relationship between genotype and phenotype,so as to provide basis for clinical precise treatment and genetic counseling.Methods:A case of NF1 complicated with skull defect in the Department of Neurosurgery of the second hospital of Shanxi Medical University was collected for medical history,physical examination,laboratory examination and genetic testing of family members;The peripheral and venous blood samples of patients and their families were collected,and the whole exome sequencing(WES)method was used to perform quality control and mutation identification on the data through bioinformatics,so as to screen out the suspected pathogenic gene loci.Then,Sanger sequencing was used to verify whether it was consistent with family Co isolation,and disease prediction and protein conservation analysis were carried out to determine the suspected pathogenic genes of the family.Results:1.The patient,male,21 years old,was admitted to hospital due to head mass and partial skull defect.History: There was a mass protruding on the right side of the head at birth,no pain,redness,headache,nausea,vomiting,breath tightness,chest tightness and other symptoms.Clinical manifestation: intelligence and development are normal,trunk and limbs can be seen multiple scattered in the distribution of brown patches,patch shape size is different,the boundary is clear,without eminence,the surface is smooth,partial pigment is not evenly distributed,bilateral armpit and groin can be seen freckle-like pigmentation.2.CT examination of skull: scalp tumor;The right occipital skull is defective,and the bone cortex of the remaining skull is continuous;Bilateral frontal sinus,maxillary sinus and ethmoid sinusitis.MRI: punctate T1 and long T2 signal shadow can be seen in the pressure part of corpus callosum,and T2 flair shows high signal,that is,T2 high signal lesion in the pressure part of corpus callosum,which is consistent with clinical neurofibromatosis.No iris Lisch nodule was found in ophthalmic slit lamp examination.Abdominal color Doppler ultrasound,chest Dr photography,heart,diaphragm,lung and 12 lead ECG showed no abnormalities.Skin pathological examination showed neurofibroma,combined with clinical analysis.Clinical diagnosis:neurofibroma with skull defect(right temporal occipital part).3.According to the results of full exon sequencing,bioinformatics analysis and Sanger sequencing,it was found that the c.3113+1 G>A of NF1 gene in the proband and his father(Ⅱ-2、Ⅰ-2)had splice mutations.The c.3113+1 G>A splice variant of NF1 gene may be the pathogenic variant of this family.Conclusion:According to the patient’s medical history,clinical manifestations,family gene mutation detection and health information analysis,it was diagnosed as partial skull defect of type 1 neurofibroma(right temporal occipital part).The mutation of c.3113 +1G > A in NF1 gene may be the pathogenic cause of patients in this family.This study found that NF1 genotype and phenotype were co separated.