IntroductionWiedemann–Steiner syndrome (WSS) is a rare autosomal‐dominant disorder caused by KMT2A variants. The aim of this study was to characterize a novel KMT2A variant in a child with WSS and demonstrate integrated diagnostic approaches.MethodsA 3‐year‐old female with developmental delay, distinctive facial features, and anal fistula underwent whole exome sequencing (WES). RNA analysis was performed to assess splicing effects caused by a novel variant.ResultsWES identified novel heterozygous KMT2A c.5664+6T>C variant initially classified as a variant of uncertain significance. RNA analysis provided evidence of aberrant splicing (exon 20 skipping), allowing reclassification to likely pathogenic. The patient exhibited typical WSS features along with a potential novel finding of anal fistula.ConclusionThis report describes a novel non‐canonical splice site variant in KMT2A associated with WSS. RNA analysis was critical for variant reclassification. Detailed phenotypic evaluation revealed common and expanded WSS manifestations. This case highlights the importance of combining clinical assessment, DNA testing, and RNA functional assays for the diagnosis of rare genetic disorders.

中文翻译：

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Wiedemann-Steiner 综合征中一种新型 KMT2A 变异引起的异常剪接

简介维德曼-施泰纳综合征 (WSS) 是一种罕见的常染色体显性遗传疾病，由以下疾病引起：国民党2A变体。这项研究的目的是描绘一部小说的特征国民党2A方法对一名发育迟缓、面部特征独特、患有肛瘘的 3 岁女性进行全外显子组测序 (WES)。进行 RNA 分析以评估新变体引起的剪接效应。结果WES 鉴定出新的杂合子国民党2Ac.5664+6T>C变体最初被分类为意义不确定的变体。 RNA 分析提供了异常剪接（外显子 20 跳跃）的证据，从而可以重新分类为可能的致病性。该患者表现出典型的 WSS 特征以及潜在的肛瘘新发现。结论本报告描述了一种新的非典型剪接位点变异国民党2A与 WSS 相关。 RNA 分析对于变异重新分类至关重要。详细的表型评估揭示了常见和扩展的 WSS 表现。该病例强调了结合临床评估、DNA 检测和 RNA 功能测定来诊断罕见遗传性疾病的重要性。