Triplications of chromosome 1p36.3, including the genes GABRD and SKI,are associated with a developmental disorder and a facial gestalt

Triplication of chromosomal region 1p36.3 is a rare genomic rearrangement. In this report, we delineate the phenotypic spectrum associated with 1p36.3 triplications. We describe four patients with microtriplications of variable size, but with a strong phenotypic overlap, and compare them to previously described patients with an isolated triplication or duplication of this region. The 1p36.3 triplication syndrome is associated with a distinct phenotype, characterized by global developmental delay, moderate intellectual disability, seizures, behavioral problems, and specific facial dysmorphic features, including ptosis, hypertelorism, and arched eyebrows. The de novo occurrence of these microtriplications demonstrates the reduced reproductive fitness associated with this genotype, in contrast to 1p36.3 duplications which are mostly inherited and can be associated with similar facial features but with a less severe developmental phenotype. The shared triplicated region encompasses four disease-related genes of which GABRD and SKI are most likely to contribute to the phenotype.     

基于公共数据库分析GABRD基因在肾透明细胞癌组织中的表达及预后意义

目的:探讨γ-氨基丁酸A受体δ亚基（GABRD）基因在肾透明细胞癌组织中的表达及预后意义,通过富集分析初步了解GABRD基因在肾透明细胞癌中可能发挥的功能。方法:提取Oncomine和TCGA数据库中有关GABRD基因表达的数据集,进行数据挖掘。筛选GABRD基因在肾透明细胞癌中的关联基因并进行富集分析。结果:Oncomine和TCGA数据库中检索到涉及GABRD基因的研究包含肾透明细胞癌标本75例和正常组织597例。在肾透明细胞癌组织中GABRD mRNA的表达量显著高于正常组织（P＜0.01）。使用UALCAN网站分析来自TCGA数据库531例肾透明细胞癌患者发现,GABRD高表达的患者总体死亡率较高,而低表达GABRD的患者预后较好（P=0.012）。基于UALCAN网站筛选出的GABRD关联基因,富集分析发现这些基因主要涉及血管生成、肌动蛋白着丝过程、细胞连接、对生长因子的反应、小GTP酶介导的信号转导、涉及细胞分化的细胞表型等。结论:GABRD基因在肾透明细胞癌组织中呈现高表达,并与肾透明细胞癌预后相关,其共表达基因参与多个和肿瘤发生进展有关的生物过程,有望成为肾透明细胞癌的治疗靶点。     

Genes and loci involved in febrile seizures and related epilepsy syndromes

Epilepsy is a paroxysmal disorder with a cumulative incidence of about 3%. About 13% of patients with epilepsy have a history of febrile seizures (FS). Generalized epilepsy with FS plus (GEFS+) is a familial epilepsy syndrome in which patients can have classic FS, FS that persist beyond the age of 5 years (i.e., FS+), and/or epilepsy. Both genetic and environmental factors have been shown to contribute to the pathogenesis of FS and GEFS+. During the past 10 years, molecular genetic studies have contributed a great deal to the identification of genetic factors involved in FS and GEFS+. In this study we aimed to provide a comprehensive review of currently known genes for FS and GEFS+, and the methods and approaches used to identify them. We also discuss the knowledge we currently have and hypotheses regarding the effect of the mutations on their respective protein functions.