Corriveau Melina L, Korb Joshua C, Michener Sydney L, Owen Nichole M, Wilson Erica L, Kubala Jamie, Turner Alicia, Takacs Danielle S, Potocki Lorraine, Swann John W, Xue Mingshan, Dai Hongzheng, Chao Hsiao-Tuan
The Cain Pediatric Neurology Research Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, USA.
School of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Am J Med Genet A. 2025 Jun;197(6):e63975. doi: 10.1002/ajmg.a.63975. Epub 2025 Jan 30.
5q14.3 microdeletion syndrome (MIM#613443) is a neurodevelopmental disorder (NDD) involving copy number loss of multiple genes including Myocyte enhancer factor 2C (MEF2C) gene in the q14.3 region of chromosome 5. Chromosomes 5 and 15 chromothripsis involving 5q14.3 was previously reported in one individual with developmental epileptic encephalopathy (DEE). A complex chromothripsis between chromosomes 3, 5, 7, 9, and 18 that involved 5q14.3 was also reported in a pregnancy complicated by brain and kidney anomalies on fetal ultrasound. Here, we report chromothripsis of chromosomes 3q and 5q involving 5q14.3 in a three-year-old female with Lennox-Gastaut syndrome. The chromosomes 3q and 5q chromothripsis was found by trio genome sequencing (GS) and confirmed by fluorescent in situ hybridization (FISH). Notable clinical findings include medically refractory seizures, global developmental delay, increased fluid-attenuated inversion recovery (FLAIR) signal in the left inferior temporal gyrus, and dysmorphic features. Chromothripsis of chromosomes 3 and 5 was previously recognized in renal cell carcinomas. To the best of our knowledge, this is the first reported case of chromosomes 3q and 5q chromothripsis leading to a developmental epileptic encephalopathy (DEE) due to disruption of 5q14.3. These findings expand chromosomes 3 and 5 chromothripsis as a genomic mechanism underlying 5q14.3 microdeletion syndrome.
5q14.3微缺失综合征（MIM#613443）是一种神经发育障碍（NDD），涉及5号染色体q14.3区域多个基因的拷贝数缺失，包括肌细胞增强因子2C（MEF2C）基因。先前有报道称，一名患有发育性癫痫性脑病（DEE）的个体存在涉及5q14.3的5号和15号染色体的染色体碎裂。在一例胎儿超声检查发现合并脑和肾异常的妊娠中，也报道了涉及5q14.3的3号、5号、7号、9号和18号染色体之间的复杂染色体碎裂。在此，我们报告了一名患有Lennox-Gastaut综合征的三岁女性中涉及5q14.3的3号和5号染色体的染色体碎裂。通过三联体基因组测序（GS）发现了3号和5号染色体的染色体碎裂，并通过荧光原位杂交（FISH）进行了确认。显著的临床发现包括药物难治性癫痫发作、全面发育迟缓、左侧颞下回液体衰减反转恢复（FLAIR）信号增加以及畸形特征。3号和5号染色体的染色体碎裂先前在肾细胞癌中被识别。据我们所知，这是首例因5q14.3破坏导致发育性癫痫性脑病（DEE）的3号和5号染色体染色体碎裂的报道病例。这些发现扩展了3号和5号染色体染色体碎裂作为5q14.3微缺失综合征潜在基因组机制的认识。
