Analysis of neurofibromatosis 1 gene mutation in a family with neurofibromatosis and its clinical significance / 中华神经科杂志

ABSTRACT

To screen the pathogenic mutation location in a genetic family with the neurofibromatosis (NF1) by the next generation sequencing and analyze the clinical phenotype,Illumina Miseq sequencing was applied to capture and analyze the target regions of NF1 family's probands,and furtherly find out the suspicious mutations,as well as to verify the family members by Sanger sequencing.Two rare variants were identified in proband,including the heterozygous missense mutation c.C3649T (p.P1217S) in KIF1B gene and the missense mutation c.T6311C (p.L2104P) on exon 41 of NF1 gene (NM_000267.3).The amino acid at position 2104 was found to be changed from leucine to proline in NF1.The protein prediction SIFT and Polyphen-2 values were 0,0.997,which predicted a conformational change in the encoded protein and eventually affected its function.The mutation c.T6311C in NF1 gene was detected in all patients in this family,which showed genetic co-segregation.The clinical phenotype was neurofibroma in the spinal canal.There were no café au lait spots,iris Lisch nodules,scoliosis,tinnitus,heating loss,or elevated intracranial pressure.The missense mutation c.T6311C (p.L2104P) in NF1 gene might be the genetic cause of this hereditary disease of neurofibromatosis.