Cai Qianyun, Feng Fan, Wang Haijiao, Tian Yanmei, Luo Rong, Yang Fan, Qian Xiao, Zhou Zhongjie
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Department of Pediatrics, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, Sichuan, China.
Int J Dev Neurosci. 2025 Apr;85(2):e70012. doi: 10.1002/jdn.70012.
O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant disorder associated with KMT2E gene variants. ODLURO syndrome is characterized mainly by developmental delay, intellectual disability and macrocephaly or microcephaly; in some patients, it may manifest as autism or epilepsy.
Trio whole-exome sequencing was performed on a female infant with unexplained West syndrome and developmental regression. A de novo splicing variant in the KMT2E gene was identified. The effects of this variant were analysed via a minigene splice assay and in vitro reverse transcription PCR.
The patient presented with spasmodic seizures and developmental delay at 6 months of age. The video electroencephalogram (EEG) displayed hypsarrhythmia. Brain MRI revealed abnormal signals around the lateral ventricles and decreased white matter volume. A novel splicing variant in the KMT2E gene (NM_182931.3: c.1248_1248+9del) was identified in our proband. Sanger sequencing confirmed that the variant was not inherited from her parents. The in vitro minigene assay confirmed that c.1248_1248+9del resulted in exon 12 skipping.
To our knowledge, this is the first definite report of ODLURO syndrome with West syndrome as the original manifestation. The deleterious effects of KMT2E c.1248_1248+9del were demonstrated in our proband. Splicing variants in the KMT2E gene are rare, and our study expands the phenotype and genotype of ODLURO syndrome. Additional studies are needed to explore the genotype-phenotype correlations of this disease.
奥唐奈-卢里亚-罗丹（ODLURO）综合征是一种与KMT2E基因变异相关的常染色体显性疾病。ODLURO综合征主要特征为发育迟缓、智力残疾以及巨头畸形或小头畸形；部分患者可能表现为自闭症或癫痫。
对一名患有不明原因韦斯特综合征和发育倒退的女婴进行三联体全外显子测序。鉴定出KMT2E基因中的一个新生剪接变异。通过小基因剪接试验和体外逆转录PCR分析该变异的影响。
该患者在6个月大时出现痉挛性癫痫发作和发育迟缓。视频脑电图（EEG）显示高峰节律紊乱。脑部MRI显示侧脑室周围信号异常，白质体积减小。在我们的先证者中鉴定出KMT2E基因中的一个新的剪接变异（NM_182931.3: c.1248_1248+9del）。桑格测序证实该变异并非遗传自其父母。体外小基因试验证实c.1248_1248+9del导致外显子12跳跃。
据我们所知，这是首例以韦斯特综合征为首发表现的ODLURO综合征的确切报告。我们的先证者中证实了KMT2E c.1248_1248+9del的有害影响。KMT2E基因中的剪接变异罕见，我们的研究扩展了ODLURO综合征的表型和基因型。需要进一步研究以探索该疾病的基因型-表型相关性。
