Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Via dei Giacinti 2, 56128 Pisa, Italy.
Molecular Medicine, IRCCS Fondazione Stella Maris, Via dei Giacinti 2, 56128 Pisa, Italy.
Genes (Basel). 2024 Apr 25;15(5):548. doi: 10.3390/genes15050548.
(MIM #602075) is a relatively new gene reported only in recent years in association with neurodevelopmental disorders characterized by variable facial dysmorphisms, global developmental delay, poor or absent speech, altered electroencephalogram (EEG), and brain abnormalities on imaging. To date about thirty variants in forty-four patients/children have been described, with a heterogeneous spectrum of clinical manifestations. In the present study, we describe a new patient affected by mild intellectual disability, speech disorder, and non-specific abnormalities on EEG and neuroimaging. Family studies identified a new de novo frameshift variant c.1818delG (p.(Gln606Hisfs*101)) in . To better define genotype-phenotype associations in the different types of reported variants, we reviewed clinical data from our patient and from the literature and compared manifestations (epileptic activity, EEG abnormalities and abnormal brain imaging) due to missense variants versus those attributable to loss-of-function/premature termination variants. Our analyses showed that the latter variants are associated with less severe, non-specific clinical features when compared with the more severe phenotypes due to missense variants. These findings provide new insights into -related disorders.
（MIM #602075）是一种近年来才报道的相对较新的基因，与神经发育障碍有关，其特征为不同程度的面部畸形、全面发育迟缓、言语障碍、脑电图（EEG）改变以及影像学上的脑异常。迄今为止，已有约三十种变异在四十四个患者/儿童中被描述，临床表现具有异质性。在本研究中，我们描述了一名新的患者，其表现为轻度智力障碍、言语障碍以及 EEG 和神经影像学上的非特异性异常。家系研究发现了一个新的无义变异 c.1818delG（p.（Gln606Hisfs*101））。为了更好地定义不同类型报道的 变异的基因型-表型相关性，我们回顾了我们的患者和文献中的临床数据，并比较了错义变异引起的表现（癫痫活动、EEG 异常和异常脑成像）与功能丧失/提前终止变异引起的表现。我们的分析表明，与错义变异引起的更严重表型相比，后一种变异与不那么严重、非特异性的临床特征相关。这些发现为 -相关疾病提供了新的见解。
