摘要
目的分析1例31岁男性患者因LMNA基因杂合突变导致非典型Werner综合征的临床及遗传学资料,并分析该突变的致病性。方法对患者进行体格及各项检查、皮肤活检,同时提取患者及其父母外周血中的DNA物质,进行全外显子测序(whole exome sequencing,WES)明确致病基因,并通过Sanger测序法验证检出变异,对检出变异进行生物信息学预测。结果患者存在早老,“小鸟”样面容,脂肪萎缩,皮肤色素沉着,胰岛素抵抗等临床表现和生化异常。全外显子测序结果提示患者LMNA(Lamin A)基因1号外显子上存在一个c.G139T(p.D47Y)杂合错义变异,其父母无该基因突变,为新发突变。多种统计方法预测出该变异会对基因或基因产物造成有害影响。结论结合患者临床表现,LMNA基因c.G139T(p.D47Y)可能为该患者的致病基因,该结果可为患者家系的遗传咨询和产前诊断提供依据。
Objective To analyze the clinical phenotype and genetic characteristics of a 31-year-old male patient with atypical Werner syndrome due to missense mutation of LMNA gene and explore its pathogenicity.Methods Medical history,physical examination,and skin biopsy were performed on the patients.Meanwhile,DNA was extracted from the peripheral blood samples of the patient and his parents.Whole exome sequencing(WES)was carried out to detect the pathogenic variant.Candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results The patient had clinical manifestations and biochemical abnormalities like premature aging,bird-like face,fat atrophy,skin pigmentation,insulin resistance,and so on.A heterozygous missense mutation of c.G139T(p.D47Y)in the first exon of LMNA gene in the patient was detected by WES,but not in his parents.It was predicted deleterious effects on genes or gene products by a variety of statistical methods(PP3).Conclusions Combined with the patient's clinical manifestations,LMNA gene c.G139T(p.D47Y)might be the pathogenic gene of the patient,which can provide a basis for genetic counseling and prenatal diagnosis of the patient's family.
作者
牛瑞芳
袁慧娟
李家大
郑瑞芝
NIU Rui-fang;YUAN Hui-juan;LI Jia-da;ZHENG Rui-zhi(Department of Endocrinology,Henan Provincial People's Hospital,People's Hospital of Zhengzhou University,People's Hospital of Henan University,Zhengzhou 450003,China;Center for Medical Genetics,Central South University,Changsha 410013,China)
出处
《中华骨质疏松和骨矿盐疾病杂志》
CSCD
北大核心
2023年第1期16-22,共7页
Chinese Journal Of Osteoporosis And Bone Mineral Research
