Mutations analysis of SPG11 gene in Chinese Han patients with hereditary spastic paraplegia / 中华神经科杂志

ABSTRACT

Objective To identify disease-causing mutations in a large panel of Chinese Han patients with hereditary spastic paraplegia(HSP).Methods The coding sequence of the SPG11 gene in the probands of 28 families with ARHSP and 14 sporadic HSP patients was analyzed,and the identified changes in the sequence were tested to exclude being a benign polymorphism by sequencing 200 chromosomes from normal controls.Results Identified 13 causative mutations in SPG11 gene in 7 ARHSP and 3 sporadic HSP The mutations werec.5977C>T/p.Q1993X、c.4668T>A/p.Y1556X、c.6898_6899delCT/p.L2300AfsX23.38、c.3719_3720delTA/p.11240VfsX263、c.733_734delAT/p.M245VfsX246、c.7088_7089insATTA/p.Y2363X、c.2163_2164insT/p.1722Yfsx731、c.7101-7102insT/p.K2368X、c.6790_6791insC/p.12264PfsX2339、c.654_655delinsG/p.S218RfsX219、c.7151+4_7151+7delAGTA/p.K2384fsX2386、c.6355-21_6355-18delTCT、c.3004C>T/p.G1002X.Among them,12 were novel mutations.The rate of mutation in the SPG11 gene was 25.0%(7/28)in ARHSP,6/6 in ARHSP-TCC and 3/14 in sporadic cases.Conclusions In Chinese Han population,patients with ARHSP-TCC and sporadic HSP-TCC should be screened for SPG11.Sequencing of the SPG11 gene in these patients with is valuable for clinical diagnostic testing.