Genetic Diagnosis And Clinical Analysis Of Three Families Of Orbital Type Ⅰ Neurofibroma

Objective:Diabetic Three family lines collected with clinical diagnosis of Neurofibromatosis type 1(NF1)were tested using whole-exome sequencing technology to identify the causative genes and mutation loci and to summarize the experience in combination with treatment protocols.Methods: Three family lines with a clinical diagnosis of NF1 were collected;family line 1 included two patients and one normal family member,family line 2included two patients and three normal family members,and family line 3 included one patient and one normal family member.A detailed ophthalmologic examination,which included slit lamp microscopy,preoptic segmental photography,visual field,intraocular pressure,visual acuity,ocular A ultrasound,and MRI,was performed on the patients and the participating relatives,and their medical history was asked and their clinical signs and morbidity characteristics were analyzed.After obtaining the consent of the patient and family members and signing the relevant informed consent forms,peripheral venous blood was drawn from the patient and some family members,and genomic DNA was extracted,and whole-exome capture high-throughput sequencing technology was used to screen out the causative genes and mutation loci,and different treatment plans were given according to the situationResults: After detailed ophthalmologic examination,the NF1 combined with optic glioma(OPG)was clearly identified in the preclear in family 1,while the rest of the family members had no abnormal clinical manifestations.A heterozygous shift mutation c.6641 del G(p.Arg2214Asnfs*30)was found in the NF1 gene of the preexisting patient in family 1,whose mother also had the disease and had the same pathogenic mutation;after gamma knife treatment,the patient’s visual acuity and visual field were restored to some extent,and the visual field defect was improved compared with before.In family line 2,combined with the results of whole exon sequencing,the heterozygous shift mutation c.7240-7241 del AG(p.Ser2414Argfs*12)was found in the NF1 gene of the prefactor and his diseased brother,while the rest of the family members had no abnormal clinical manifestations and were followed up for a long time;in family line 3,it was found that the prefactor got the c.2570 del(p.Asn857llefs*21)heterozygous shift mutation in the NF1 gene was found in family3,and the bioinformatic analysis confirmed that this mutation was the first one found,and the other family members of the family were normal,and their appearance improved significantly after surgical treatment.Conclusions: 1.This study detected heterozygous shift mutations in the NF1 gene in all three families by whole-exome capture high-throughput sequencing,of which c.2570del(p.Asn857llefs*21)was reported for the first time worldwide,further clarifying the diagnosis at the genetic level.2.This study also lays the foundation for future prenatal diagnosis,genetic counseling and analysis of the correlation between genotype and phenotype in the three families.