PDF(Pubmed)
Abstract：
UNASSIGNED: Snijders Blok-Campeau syndrome (SNIBCPS) is a rare genetic disorder characterized by facial abnormalities, hypotonia, macrocephaly, and global developmental delay (GDD) caused by mutations in CHD3 gene. There is limited information on SNIBCPS and few studies on its pathogenic gene CHD3.
UNASSIGNED: We utilized whole-exome sequencing, in vitro minigene splicing assay analysis, and construction of protein models to validate the suspected pathogenic mutation. In addition, the PubMed database was searched using the keywords \"Snijders Blok-Campeau syndrome,\" \"CHD3,\" or \"SNIBCPS\" to summarize the gene mutations and clinical phenotypic characteristics of children with SNIBCPS.
UNASSIGNED: We identified a non-frameshift variant c.3592_c.3606delGCCAAGAGAAAGATG, a splice site variant c.1708-1G>T, and two missense variants, c. 2954G>C (p.Arg985Pro) and c.3371C>T (p.A1124V), in CHD3 variants with SNIBCPS. Importantly, the c.3592_c.3606delGCCAAGAGAAAGATG, c.1708-1G>T, and c.3371C > T (p.A1124V) loci were not reported, and the children in this study also had phenotypic features of unibrow, transverse palmar creases, tracheal bronchus, and hypomelanosis of Ito (HI). The c.1708-1G>T classical splicing mutation leads to abnormal shearing of mRNA, forming a truncated protein that ultimately affects gene function.
UNASSIGNED: Our findings have expanded the spectrum of genetic variants and clinical features in children with SNIBCPS. Splicing analysis of CHD3 is an important method to understand the pathogenesis of spliced cells.
UNASSIGNED: We utilized whole-exome sequencing, in vitro minigene splicing assay analysis, and construction of protein models to validate the suspected pathogenic mutation. In addition, the PubMed database was searched using the keywords \"Snijders Blok-Campeau syndrome,\" \"CHD3,\" or \"SNIBCPS\" to summarize the gene mutations and clinical phenotypic characteristics of children with SNIBCPS.
UNASSIGNED: We identified a non-frameshift variant c.3592_c.3606delGCCAAGAGAAAGATG, a splice site variant c.1708-1G>T, and two missense variants, c. 2954G>C (p.Arg985Pro) and c.3371C>T (p.A1124V), in CHD3 variants with SNIBCPS. Importantly, the c.3592_c.3606delGCCAAGAGAAAGATG, c.1708-1G>T, and c.3371C > T (p.A1124V) loci were not reported, and the children in this study also had phenotypic features of unibrow, transverse palmar creases, tracheal bronchus, and hypomelanosis of Ito (HI). The c.1708-1G>T classical splicing mutation leads to abnormal shearing of mRNA, forming a truncated protein that ultimately affects gene function.
UNASSIGNED: Our findings have expanded the spectrum of genetic variants and clinical features in children with SNIBCPS. Splicing analysis of CHD3 is an important method to understand the pathogenesis of spliced cells.
摘要：
■SnijdersBlok-Campeau综合征（SNIBCPS）是一种罕见的遗传性疾病，以面部异常为特征，低张力,大头畸形,CHD3基因突变引起的全球发育迟缓(GDD)。关于SNIBCPS的信息有限，对其致病基因CHD3的研究很少。
■我们利用了全外显子组测序，体外小基因剪接分析，并构建蛋白质模型以验证可疑致病突变。此外,使用关键字\"SnijdersBlok-Campeau综合征搜索PubMed数据库，“CHD3”或“SNIBCPS”总结SNIBCPS患儿的基因突变和临床表型特征。
■我们确定了一个非移码变体c.3592_c.3606delGCCAAGAAGATG，剪接位点变异体c.1708-1G>T,和两个错觉变体，C.2954G>C（第Arg985Pro）和c.3371C>T（p。A1124V),在具有SNIBCPS的CHD3变体中。重要的是,c.3592_c.3606delGCCAAGAGAAAGATG，c.1708-1G>T，和c.3371C>T（p。A1124V)位点未被报道，这项研究中的儿童也有单眉的表型特征，手掌横向折痕，气管支气管，和伊藤低黑素病（HI）。c.1708-1G>T经典剪接突变导致mRNA的异常剪切，形成最终影响基因功能的截短蛋白。
■我们的发现扩大了SNIBCPS患儿的遗传变异和临床特征的范围。CHD3的剪接分析是了解剪接细胞发病机制的重要方法。
■我们利用了全外显子组测序，体外小基因剪接分析，并构建蛋白质模型以验证可疑致病突变。此外,使用关键字\"SnijdersBlok-Campeau综合征搜索PubMed数据库，“CHD3”或“SNIBCPS”总结SNIBCPS患儿的基因突变和临床表型特征。
■我们确定了一个非移码变体c.3592_c.3606delGCCAAGAAGATG，剪接位点变异体c.1708-1G>T,和两个错觉变体，C.2954G>C（第Arg985Pro）和c.3371C>T（p。A1124V),在具有SNIBCPS的CHD3变体中。重要的是,c.3592_c.3606delGCCAAGAGAAAGATG，c.1708-1G>T，和c.3371C>T（p。A1124V)位点未被报道，这项研究中的儿童也有单眉的表型特征，手掌横向折痕，气管支气管，和伊藤低黑素病（HI）。c.1708-1G>T经典剪接突变导致mRNA的异常剪切，形成最终影响基因功能的截短蛋白。
■我们的发现扩大了SNIBCPS患儿的遗传变异和临床特征的范围。CHD3的剪接分析是了解剪接细胞发病机制的重要方法。
