Case Report: A Novel GNB1 Mutation Causes Global Developmental Delay With Intellectual Disability and Behavioral Disorders.
Case Report: A Novel GNB1 Mutation Causes Global Developmental Delay With Intellectual Disability and Behavioral Disorders.
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DOI：
10.3389/fneur.2021.735549
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发表时间：
2021
影响因子：
3.4
通讯作者：
Teixeira-Castro A
中科院分区：
文献类型：
--
作者：
Da Silva JD;Costa MD;Almeida B;Lopes F;Maciel P;Teixeira-Castro A
神经发育疾病大多表现为神经和精神症状，从非常轻微到非常严重。虽然大多数神经发育疾病的病因尚不清楚，但潜在的遗传原因的发现正在迅速增加，目前有数百个基因被认为是致病基因。在这里，我们报告一个临床病例，患者患有以前未被诊断出的综合征，包括严重的全球发育迟缓、智力残疾和行为障碍(如注意力缺陷/多动障碍、自闭症谱系障碍和反复发作的攻击性行为)。经过基因检测，在编码G蛋白亚基β1的GNB1基因中发现了一个致病变异。在已发表的58例GNB1脑病病例中，以前没有报道过这种变异(c.217G和gt；A，p.A73T)。然而，它定位于外显子6和7的突变热点，88%的错义突变发生在该区域。一个电子模型预测，这种突变很可能扰乱GNB1蛋白的WD40结构域，这是GNB1蛋白与其他G蛋白相互作用所必需的，从而也是下游信号转导所必需的。总之，我们报告了另一例携带新突变的GNB1脑病患者，朝着更好地了解其临床表现和该疾病治疗的前景发展又迈进了一步。
Diseases of neurodevelopment mostly exhibit neurological and psychiatric symptoms that go from very mild to extremely severe. While the etiology of most cases of neurodevelopmental disease is still unknown, the discovery of underlying genetic causes is rapidly increasing, with hundreds of genes being currently implicated as disease-causing. Here, we report a clinical case of a patient with a previously undiagnosed syndrome comprising severe global developmental delay, intellectual disability, and behavioral disorders (such as attention-deficit/hyperactivity disorder, autism spectrum disorder and recurrent bouts of aggressive behavior). After genetic testing, a pathogenic variant was detected in the GNB1 gene, which codes for the G-protein subunit β1. The detected variant (c.217G>A, p.A73T) has not been previously reported in any of the 58 published cases of GNB1 encephalopathy. However, it localizes to the mutational hotspot in exons 6 and 7 in which 88% of all missense mutations occur. An in silico model predicts that this mutation is likely to disrupt the WD40 domain of the GNB1 protein, which is required for its interaction with other G-proteins and, consequently, for downstream signal transduction. In conclusion, we reported an additional GNB1 encephalopathy patient, bearing a novel mutation, taking another step toward a better understanding of its clinical presentation and prospective development of treatments for the disease.
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影响因子：
7.3
作者：
Tesmer JJ;Tesmer VM;Lodowski DT;Steinhagen H;Huber J
通讯作者：
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影响因子：
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