纯合区域/单亲二体的判定及临床咨询原则

Clinical practice guidelines for the diagnosis of regions of homozygosity and uniparental disomy

单亲二体(uniparental disomy,UPD)在人群中的发生率可达1/2000,目前数据库收录的UPD报道约有4170例。由于印记基因的表达异常,涉及6、7、11、14、15、20号染色体的UPD可导致明确的印记疾病,而其他染色体的UPD大多不会对个体产生明显的影响,除非UPD所涉及的纯合区域(regions of homozygosity,ROH)内的基因纯合变异导致隐性遗传病。对UPD及ROH的正确分析和解读有助于对其临床意义进行准确的判断,本文重点对ROH、UPD相关概念、形成机制、致病原理及数据判定原则和分析流程等进行阐述,希望对临床规范分析和解读此类数据提供帮助。

The overall prevalence of uniparental disomy(UPD)across all chromosomes was estimated to be around one birth in 2000.To date,more than 4170 UPD cases have been registered.UPD for chromosomes 6,7,11,14,15,and 20 can result in clinically recognizable imprinting disorders due to abnormal levels of imprinted gene expression.For other chromosomes,the clinical consequences associated with UPD are not apparent,unless when a recessive genetic disorder is unmasked by UPD or regions of homozygosity(ROH).A clinical practice guideline will assist in strengthening the precise analysis and interpretation of the clinical significance of ROH/UPD.This guideline summarizes the conception,mechanism and clinical consequences of ROH/UPD,as well as the principles for data analysis,with an aim to standardize the clinical application and data interpretation.