Clinical Characteristics Of A Family With Tuberous Sclerosis And Discovery Of New Mutation Sites Of TSC2 Gene

[Objective] Based on a family with tuberous sclerosis,the purpose of this study is to analyze its clinical characteristics,look for its pathogenic gene mutation sites,distinguish between the family with or without the disease,provide a basis for the diagnosis of TSC,help for the family with genetic counseling.[Methods] We collected clinical data of probands and improved relevant auxiliary examinations.We investigated the health of all members of the family,filtrated suspected members of TSC,and drew a family tree.Peripheral venous blood 3-4ml came from the proband and other members of the family?parents,sister,brother,aunt?.The proband was detected by the combination of whole exon sequencing?IDT chip?and MLPA.If a mutation site is found,the proband and its family members were verified by Sanger sequencing.Then it is verified in the normal human gene database to rule out the possibility of polymorphism.[Results] 1.Clinical phenotype and results of auxiliary examination : the proband has epilepsy as the first symptom.She was 13 years old,was 110 cm tall,weighed 20 kg,significantly shorter than her peers,and lower intelligence.Multiple skin changes were observed,including three depigmentation spots and squalor skin on the left shoulder.There were toenail fibromas on both feet in the mother of the proband.She is normal intelligence,no epilepsy,no depigmentation and other skin changes.Others in the family behaved normally.The electroencephalogram?EEG?of the proband showed that during the period of sleep,a single wave of high amplitude tip slow compound wave and spines slow compound wave appeared repeatedly in the right or left anterior and middle temporal lead.Cranial CT showed multiple low-density shadows in bilateral frontal lobe and right temporal lobe,multiple calcifications in right basal ganglia,frontal lobe,cerebellar hemisphere and bilateral cerebral ventricle.Its nature is to be determined: tuberous sclerosis? Bilateral lateral ventricles enlarged;Large cistern or cistern arachnoid cysts may be present.CT of chest and abdomen showed multiple hamartomas of liver and left kidney.Multiple osteosclerosis of thoracolumbar and bilateral ilium;Consider multisystem changes in tuberous sclerosis.2.Gene test results: c.2983₂984 insC chr16-2129046?p.l995 pfs *11?heterozygous Mutation in The TSC2 Gene was found in the proband,which was not reported in The Human Gene Mutation Database?HGMD?.It is not included in the normal human gene database.Pedigree validation showed that this heterozygous mutation originated in the proband mother.Other members of the family?father,sister,brother,aunt?showed no mutation at this site.[Conclusion] The proband is a patient with clinically confirmed TSC.The proband and his mother detected a heterozygous mutation in the TSC2 gene c.2983₂984insC?p.L995 Pfs * 11?,which is a new mutation site;2.The proband and his mother have the same mutation,different clinical manifestations,and clinical heterogeneity.