Vincent Krista M, Bourque Danielle K
Department of Medical Genetics, CHEO, Ottawa, Ontario, Canada.
Division of Metabolics and Newborn Screening, Department of Pediatrics, CHEO, Ottawa, Ontario, Canada.
Brain Dev. 2023 Apr;45(4):244-249. doi: 10.1016/j.braindev.2023.01.003. Epub 2023 Jan 27.
CUL3-related neurodevelopmental disorder is a recently described rare genetic condition characterized by global developmental delay and intellectual disability. Five affected individuals have been reported worldwide. The molecular and phenotypic spectrum of the disorder has yet to be fully elucidated. Splice variants in CUL3 are a well-described cause of pseudohypoaldosteronism type IIE; however, splice variants have not been associated with the neurodevelopmental disorder. We report the first individual with a neurodevelopmental disorder attributed to a CUL3 splice site variant.
The patient presented with congenital developmental dysplasia of the hip and global developmental delay. A de novo splice site variant (c.379-2A > G) was identified in CUL3 and is predicted to abolish the acceptor splice site.
This is the first report of an individual with a splice site variant causing CUL3-related neurodevelopmental disorder and expands our understanding of this rare condition.
CUL3相关神经发育障碍是一种最近被描述的罕见遗传疾病，其特征为全面发育迟缓及智力残疾。全球已报道了5例受累个体。该疾病的分子和表型谱尚未完全阐明。CUL3中的剪接变体是IIE型假性醛固酮减少症的一个已充分描述的病因；然而，剪接变体尚未与这种神经发育障碍相关联。我们报告了首例因CUL3剪接位点变体导致神经发育障碍的个体。
该患者表现为先天性髋关节发育不良和全面发育迟缓。在CUL3中鉴定出一个新生剪接位点变体（c.379-2A>G），预计该变体将消除受体剪接位点。
这是首例关于由剪接位点变体导致CUL3相关神经发育障碍个体的报告，并扩展了我们对这种罕见疾病的认识。
