新疆地区维吾尔族成骨不全九例患儿基因型与表型分析

Genotypes and phenotypes of nine Uygur children with osteogenesis imperfecta in Xinjiang

目的探讨新疆地区维吾尔族儿童成骨不全基因变异谱系及临床表型特点.方法回顾性分析2013年1月至2017年12月新疆医科大学第一附属医院儿科就诊的9例(男4例、女5例)维吾尔族成骨不全患儿的临床资料,按照经典Sillence分型进行临床分型.检测成骨不全相关基因,利用美国医学遗传学和基因组学协会指南、InterVar、Alamut功能软件评估变异致病性,分析基因变异谱系特点.结果9例患儿年龄3岁6月龄~15岁,临床表现为反复骨折、骨骼畸形、矮小、蓝巩膜、听力异常、牙本质发育不全、关节韧带松弛.其中成骨不全Ⅲ型6例、Ⅳ型3例.9例患儿中共发现3种基因(COL1A1、COL1A2和SERPINF1)的9个候选变异,其中5个变异位点为国际首次报道,经评估均为可能致病性变异.结论新疆维吾尔族成骨不全临床表型复杂多样,但均有骨折及骨骼畸形.基因型与国内外报道有差异,SERPINF1基因可能在维吾尔族人群中更为高发,维吾尔族成骨不全的遗传异质性及独特的基因变异谱系,进一步为成骨不全的基因型与表型相关性提供了依据.

Objective To explore the genotypes and phenotypes of osteogenesis imperfecta(OI)in Xinjiang Uygur children.Methods The history of nine Uygur children with OI who were hospitalized in First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2017 were retrospectively reviewed.They were classified into 4 types according to the classical Sillence classification.The genes associated with OI were detected,and the pathogenic variation was assessed by InterVar and Alamut software according to the American College of Medical Genetics and Genomics(ACMG)recommendations.The phenotypes of children with different genotypes were further analyzed.Results Nine cases aged 3 years and 6 monthes to 15 years were all clinically diagnosed as OI,the clinical manifes tations were repeated fractures,skeletal deformities,short stature,blue sclera,abnormol hearing,hypoplasia of dentin,and relaxation of Joint ligaments,among whom 6 was typeⅢOI,3 were typeⅣOI.Nine mutations in 3 genes(COL1A1,COL1A2,and SERPINF1)were detected,and 5 of them were first reported and were all pathogenic variations.Conclusions The cinical phenotypes of osteogenesis imperfecta in Xinjiang Uygur are complex and varied,but all of them have fractures and skeletal deformities.Genotype is different from that reported at China and abroad,and the SERPINF1 gene may have a higher incidence in Uyghur population.The genetic heterogeneity and unique gene variation pedigree of Uyghur osteogenesis imperfecta defects further provide a basis for the correlation between genotype and phenotype of osteogenesis defects.