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Abstract：
Warburg micro syndrome (WARBM) is a rare autosomal recessive disorder characterized by microcephaly, cortical dysplasia, intellectual disability, ocular abnormalities, spastic diplegia, and microgenitalia. WARBM has 4 subtypes arising from pathogenic variants in 4 genes (RAB18, RAB3GAP1, RAB3GAP2, and TBC1D20). Here, we report on a patient with a homozygous pathogenic c.665delC (p.Pro222HisfsTer30) variant in the RAB3GAP1 gene identified by whole-exome sequencing (WES) analyses. Only his father was a heterozygous carrier, and homozygosity mapping analysis of the WES data revealed large loss-of-heterozygosity regions in both arms of chromosome 2, interpreted as uniparental isodisomy. This uniparental disomy pattern could be due to paternal meiosis I nondisjunction because of the preserved heterozygosity in the pericentromeric region. This report provides novel insights, including a rare form of UPD, usage of homozygosity mapping analysis for the evaluation of isodisomy, and the first reported case of WARBM1 as a result of uniparental isodisomy.
摘要：
Warburg微综合征（WARBM）是一种罕见的常染色体隐性遗传疾病，以小头畸形为特征，皮质发育不良,智力残疾,眼部异常，痉挛性双瘫,和微生殖器。WARBM在4个基因(RAB18、RAB3GAP1、RAB3GAP2和TBC1D20)中具有由致病变体产生的4种亚型。这里,我们报道了一名纯合致病性c.665delC的患者（p。通过全外显子组测序（WES）分析鉴定的RAB3GAP1基因中的Pro222HisfsTer30）变体。只有他父亲是个杂合携带者,WES数据的纯合性作图分析显示，2号染色体的两个分支中杂合性缺失区域很大，被解释为单亲等异体性。这种单亲二分体模式可能是由于父系减数分裂I不分离，因为在着丝粒区域保留了杂合性。这份报告提供了新颖的见解，包括一种罕见的UPD,纯合性映射分析在等分体评估中的应用，以及第一例由于单亲同体而报告的WARBM1病例。
