一例3-M综合征患者的临床及分子遗传学分析

Clinical and molecular genetic analysis of a patient with 3-M syndrome

目的分析1例来自近亲婚配家系的3-M(Miller-McKusick-Malvaux)综合征患者的临床特征和基因型, 探讨其基因型与表型的关系。方法经先证者监护人同意并签署知情同意书后, 采集先证者及其父母外周血提取gDNA, 进行染色体微阵列分析及医学外显子组测序与父母验证。结果 CytoScan 750K array分析发现先证者存在247.1 Mb的纯合区域;医学外显子组测序发现在患者的纯合区域包含OBSL1基因c.458dupG纯合变异, 该变异遗传自父母。根据ACMG/AMP遗传变异判断标准和指南, 该变异为致病性变异(PVS1+PM2+PP4), 目前仅有1例文献报道。结论隐性脊柱裂、下眼睑脂肪垫可能是OBSL1基因c.458dupG变异的特殊表型, 上述结果可为研究2型3-M综合征基因型与表型的关系提供参考。

Objective To analyze the clinical features and molecular genetic etiology of a patient with3-M(Miller McKusick Malvaux)syndrome from a consanguincous parentage family,and to explore therelationship between genotype and phenotype.Methods After the consent of the proband's guardian and theinformed consent form was signed,DNA was extracted from peripheral blood samples of the proband andher parents for chromosome microarray analysis,medical exome sequencing and parental verification.ResultsA total of 247.1 Mb loss of heterozygosity was found in the proband with a CytoScan 750K array.Furthermore,a homozygous variant(c.458dupG)of the OBSLl gene was found using high-throughputsequencing,which was inherited from her parents.Based on the criteria and guidelines of genetic variation ofAmerican College of Medical Genetics and Genomics,the variant is predicted to be pathogenic(PVS1+PM2+PP4),and only one case was reported previously.Conclusion Spina bifida occulta and lower eyelid fat padmay be a special phenotype of c.458dupG variant of the OBSL1 gene.Our study may provide a usefulreference for evaluating the relationship between genotype and phenotype of 3-M syndrome type 2.