PDF(Pubmed)
Abstract：
Baker-Gordon Syndrome (BAGOS) is a genetically determined 4 (NDD), represented by a phenotypic spectrum of moderate to severe intellectual disability, resulting from mutations in the synaptotagmin 1 (SYT1) gene. Its prevalence is estimated at 1:1,000,000 and the known gene variants have indicated complete penetrance with variable expressivity. SYT1 is a membrane trafficking protein in presynaptic vesicles, which exerts a complex influence on synaptic transmission, with fundamental roles in the release of neurotransmitters and facilitators of endocytosis, impacting both neurotransmission and neuron plasticity. The current case report describes the first Brazilian male patient diagnosed at 17-year-old, and the 39th reported case globally using whole-exome sequencing. A de novo heterozygous missense mutation at chr12q:79448958 (NM_005639.2; c.1103T>C; p.Ile368Thr) in the SYT1 was found and classified as a pathogenic variant. The proband\'s clinical phenotype was compatible with BAGOS, involving behavioral changes such as irritability and severe intellectual disability. Knowledge about the mechanism of action and the extent of the genotypic and phenotypic presentations of the mutations in the SYT1 is still unfolding. Thus, we aimed to describe additional genotype-phenotype correlation for BAGOS, contributing to the expansion of the existing knowledge of such a heterogeneous ultra-rare syndrome, and, therefore, improve its diagnostic yield, case management, and therapeutic journey for future patients.
摘要：
贝克-戈登综合征(BAGOS)是一种由基因决定的4(NDD)，以中度至重度智力残疾的表型谱为代表，由突触蛋白1(SYT1)基因突变引起。其患病率估计为1：1,000,000，并且已知的基因变体已经表明具有可变表达的完全外显率。SYT1是突触前囊泡中的膜运输蛋白，对突触传递产生复杂的影响，在神经递质的释放和内吞的促进中具有基本作用，影响神经传递和神经元可塑性。目前的病例报告描述了第一位在17岁时被诊断出的巴西男性患者，全球第39例报告病例使用全外显子组测序。在SYT1中发现了chr12q：79448958（NM_005639.2；c.1103T>C；p.Ile368Thr）的从头杂合错义突变，并将其归类为致病性变体。先证者的临床表型与BAGOS相符，包括易怒和严重智力残疾等行为变化。关于SYT1突变的作用机制以及基因型和表型表现的程度的知识仍在展开。因此，我们旨在描述BAGOS的其他基因型-表型相关性，有助于扩大对这种异质性超罕见综合征的现有知识，and,因此,提高其诊断率，案件管理,和未来患者的治疗之旅。
