儿童Ⅰ型神经纤维瘤病脊柱畸形的遗传学特点及手术治疗效果研究OA北大核心

Objective To explore the genotypic characteristics of children with neurofibromatosis type 1(NF1)associated dystrophic scoliosis and summarize the outcomes of surgery.Methods Whole exome se-quencing(WES),multiplexligation-dependent probe amplification(MLPA)and whole genome Sequencing(WGS)was utilized for genotypic identification.A total of 47 children were operated for spinal deformities and the outcomes of surgery summarized by examining the clinical and imaging parameters before and after surgery.Results Twenty-three boys and 24 girls were clinically diagnosed as NF1 associated scoliosis with common symptoms including café-au-lait spots and scoliosis.NF1 mutations were detected in 43(91.5％)children,in-cluding 16 nonsense mutations,9 splicing mutations,13 frame shift mutations,2 missense mutation,2 exon dele-tions and 1 exon duplication.Initial surgical procedures included growing-rod surgery(n=30)and posterior spinal fusion(n=17).The follow-up duration was 3.6 years and Cobb angle of main curve improved from 56.0(43.0,65.0)° pre-operatively to 17.0(8.0,25.0)° at the last follow-up with an average correction rate of(68.6±17.5)％.The complications occurred in 9 patients during follow-ups.Conclusions In children with scoliosis fulfilling the clinical diagnostic criteria for NF1,the mutation detection rate of WES,MLPA,WGS was 91.5％.There is no mutation hotspot in NF1 gene.Molecular diagnosis may offer information about genetic counseling,prenatal diagnosis and eugenics.Surgery based upon patient age and severity may effectively correct spinal deformities.