Clinical Analysis And Gene Mutation Study Of Hereditary Spastic Paraplegia Type 30

Objective:Hereditary spastic paraplegia(HSP)is a rare neurodegenerative disorder characterized by insidious onset,slow progression,of both lower limbs and muscle weakness.In this study,clinical manifestations,gene sequencing analysis and bioinformatics prediction were performed on a patient with hereditary spastic paraplegia type 30(HSP30)to clarify its possible pathogenic genes,so as to enrich the mutation spectrum of KIF1 A gene in Chinese population.Provide a basis for future clinical precision treatment and genetic counseling.Methods:A sample of patients was collected from the Second Hospital of Shanxi Medical University in August 2021 for clinical consultation,including past medical history,family history,etc.;corresponding clinical examinations were performed: physical examination,electromyography,imaging,etc.;then peripheral blood was collected from the patients and their families for the next step of genetic testing.The next step is to analyze the test data by bioinformatics,screen for suspected pathogenic loci,verify them by Sanger sequencing,and perform protein conserved type analysis and pathogenicity prediction to identify the possible pathogenic genes in the family line.Results:1.The patient,male,15 years old,was admitted to the hospital due to weakness of both lower limbs for more than two years.Medical history : Clinical manifestations : the strength of both lower limbs gradually weakened,without myalgia,joint pain,and limb numbness.2.Physical examination : no obvious muscle atrophy;upper limb muscle tension was normal,lower limb muscle tension increased,upper limb muscle strength 4 + grade,lower limb proximal muscle strength 4G grade,distal 3 + grade.Double upper limb tendon reflex(+),double lower limb tendon reflex(+ + +).Foot drop,arched foot(Fig.2-1),plantar flexion grade 3,dorsiflexion grade 0.Unable to walk with toes and heels,unable to squat,abnormal gait,but all autonomous movement.3.EMG examination : EMG examination showed that nerve electrophysiology G EMG evoked potential;the motor nerve conduction velocity(MCV),terminal latency(DL)and amplitude of ulnar nerve,median nerve,tibial nerve and common peroneal nerve were within the normal range.The sensory nerve conduction velocity(SCV)and amplitude of ulnar nerve,median nerve,sural nerve and superficial peroneal nerve were the lower limit of normal range.The F wave and H reflex of the detected nerves were normal,and the electrophysiological changes of central damage were diagnosed.4.Through whole exon sequencing results,bioinformatics analysis and Sanger sequencing verification,it was concluded that the heterozygous mutation of KIF1 A gene c.110 T > C(p.I37T)occurred in the proband(II-3)of this family.The substitution of isoleucine at position 37 for threonine may affect the function of its protein products.The parents,brother and sister of the proband did not carry the same mutation,suggesting that it was a new onset.According to the relevant guidelines of the American Society of Medical Genetics and Genomics,the mutation was judged to be possibly pathogenic(PM2 + PP3 + PS2).Conclusion:In combination with the patient’s clinical consultation,genetic testing,and subsequent analysis to validate the results,hereditary spastic paraplegia was identified.c.110 T > C(p.I37T)variation in the KIF1 A gene may be the causative agent in this family of patients.