PDF(Sci-hub)
Abstract：
Intellectual developmental disorder with dysmorphic facies and ptosis is an autosomal dominant condition characterized by delayed psychomotor development, intellectual disability, delayed speech, and dysmorphic facial features, mostly ptosis. Heterozygous mutations in bromodomain and plant homeodomain (PHD) finger containing one (BRPF1) gene have been reported. In this study, whole exome sequencing (WES) was performed as a molecular diagnostic test. Bioinformatics of WES data and candidate gene prioritization identified a novel variant in heterozygous state in the exon 3 of BRPF1 gene (ENST383829: c.1054G > C and p.Val352Leu). Autosomal dominant inheritance in the family affected individuals and exclusion of non-pathogenicity in the ethnically matched healthy controls (n = 100) were performed by Sanger sequencing. To the best of our knowledge, this is the first evidence of BRPF1 variant in a Saudi family. Whole exome sequencing analysis has been proven as a valuable tool in the molecular diagnostics. Our findings further expand the role of WES in efficient disease diagnosis in Arab families and explained that the mutation in BRPF1 gene plays an important role for the development of IDDFP syndrome.
摘要：
智力发育障碍与畸形相和上睑下垂是一种常染色体显性疾病，其特征是精神运动发育延迟。智力残疾,说话延迟,和畸形的面部特征，主要是眼睑下垂。已经报道了包含一个（BRPF1）基因的溴结构域和植物同源结构域（PHD）指的杂合突变。在这项研究中,进行全外显子组测序(WES)作为分子诊断试验.WES数据和候选基因优先排序的生物信息学鉴定了BRPF1基因外显子3中处于杂合状态的新变体(ENST383829:c.1054G>C和p.Val352Leu)。通过Sanger测序，在受家庭影响的个体中进行常染色体显性遗传，并在种族匹配的健康对照（n=100）中排除非致病性。据我们所知,这是沙特家族中BRPF1变体的第一个证据。全外显子组测序分析已被证明是分子诊断中的有价值的工具。我们的发现进一步扩大了WES在阿拉伯家庭有效疾病诊断中的作用，并解释了BRPF1基因的突变在IDDFP综合征的发展中起着重要作用。
