Research Unit of Medical Genetics, Department of Medicine, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy.
Operative Research Unit of Medical Genetics, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy.
Genes (Basel). 2023 Jun 27;14(7):1353. doi: 10.3390/genes14071353.
The use of NGS technology has rapidly increased during the last decade, and many new monogenic neurodevelopmental disorders have emerged. Pathogenic variants in the neuronal gene have been recently associated with "intellectual developmental disorder, autosomal dominant 53″ (OMIM#617798), a syndrome characterized by variable clinical manifestations including mild to severe intellectual disability, delayed psychomotor development, delayed or absent speech, delayed walking, seizures, dysmorphic features and behavioral psychiatric manifestations as autism spectrum disorders, aggressive behavior, and hyperactivity. (OMIM*114078) encodes for a subunit of the calcium/calmodulin-dependent serine/threonine kinase II (CaMKII), which is predominately expressed in the brain, where it plays critical roles in synaptic plasticity, learning, and memory as well as in neuronal migration.
We hereby describe a thirty-five-year-old woman affected by severe intellectual disability with epileptic encephalopathy. We performed exome sequencing and found a de novo heterozygous variant in the gene (NM_171825.2: c.874_876delCTT; p.Lys292del), which was fully correlated with her phenotype. This is the first report of an inframe single amino acid deletion in a patient affected by intellectual developmental disorder autosomal dominant 53. The variant is predicted to affect protein structure and function and interaction with other proteins and hits a crucial functional site.
We discuss our variant in relation to previously reported variants and with the objective of delineating possible genotype-phenotype correlations.
在过去的十年中，NGS 技术的应用迅速增加，许多新的单基因神经发育障碍也相继出现。神经元基因的致病性变异最近与“常染色体显性 53 型智力发育障碍”（OMIM#617798）相关，该综合征的临床表现多样，包括轻度至重度智力障碍、精神运动发育迟缓、言语延迟或缺失、行走延迟、癫痫发作、发育异常和行为精神表现，如自闭症谱系障碍、攻击性行为和多动。（OMIM*114078）编码钙/钙调蛋白依赖性丝氨酸/苏氨酸激酶 II（CaMKII）的亚基，该激酶主要在大脑中表达，在突触可塑性、学习和记忆以及神经元迁移中发挥关键作用。
我们在此描述了一位 35 岁的女性患者，患有严重的智力障碍和癫痫性脑病。我们进行了外显子组测序，发现一个基因（NM_171825.2: c.874_876delCTT; p.Lys292del）的新生杂合变异，该变异与她的表型完全相关。这是首例报道的常染色体显性 53 型智力发育障碍患者中出现的框内单个氨基酸缺失。该变异预计会影响蛋白结构和功能，以及与其他蛋白的相互作用，并击中关键功能位点。
我们根据以前报道的变异以及明确可能的基因型-表型相关性的目的来讨论我们的变异。
