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.

中文翻译：

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Warburg 微综合征 1 由于全外显子组测序和纯合子映射检测到的 2 号染色体节段父本单亲同二体

Warburg 微综合征 (WARBM) 是一种罕见的常染色体隐性遗传疾病，其特征是小头畸形、皮质发育不良、智力障碍、眼部异常、痉挛性双瘫和小生殖器。WARBM 有 4 个亚型，由 4 个基因（RAB18、RAB3GAP1、RAB3GAP2 和 TBC1D20）的致病变异引起。在这里，我们报告了通过全外显子组测序 (WES) 分析鉴定的 RAB3GAP1 基因中具有纯合致病性 c.665delC (p.Pro222HisfsTer30) 变异的患者。只有他的父亲是杂合子携带者，WES 数据的纯合子作图分析显示 2 号染色体双臂存在大量杂合子缺失区域，解释为单亲同二体。这种单亲二体模式可能是由于父本减数分裂 I 不分离，因为在着丝粒周围区域保留了杂合性。