扩展 PRMT7 突变的临床和分子谱:3 例额外患者及综述。

Expanding the clinical and molecular spectrum of PRMT7 mutations: 3 additional patients and review.

机构信息

Laboratory of Medical Genetics, Ospedale Pediatrico Bambino Gesù, Rome, Italy.

Medical Genetics Unit, Ospedale Pediatrico Bambino Gesù, Rome, Italy.

出版信息

Clin Genet. 2018 Mar;93(3):675-681. doi: 10.1111/cge.13137. Epub 2018 Feb 5.

Abstract

Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyze the transfer of methyl groups from S-adenosyl-l-methionine to nitrogen atoms on arginine residues. Arginine methylation is involved in multiple biological processes, such as signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. Currently, 7 patients have been described harboring compound heterozygous or homozygous variants in the PRMT7 gene, causing a novel intellectual disability syndrome, known as SBIDDS syndrome (Short Stature, Brachydactyly, Intellectual Developmental Disability, and Seizures). We report on 3 additional patients from 2 consanguineous families with severe/moderate intellectual disability, short stature, brachydactyly and dysmorphisms. Exome sequencing revealed 2 novel homozygous mutations in PRMT7. Our findings expand the clinical and molecular spectrum of homozygous PRMT7 mutations, associated to the SBIDDS syndrome, showing a possible correlation between the type of mutation and the severity of the phenotype.

摘要

蛋白质精氨酸甲基转移酶 7(PRMT7)是一类能够催化 S-腺苷甲硫氨酸的甲基转移到精氨酸残基氮原子上的酶的家族成员。精氨酸甲基化参与多种生物学过程,如信号转导、mRNA 剪接、转录调控、DNA 修复和蛋白质易位。目前,已有 7 名患者被描述在 PRMT7 基因中携带复合杂合或纯合变异,导致一种新的智力发育障碍综合征,称为 SBIDDS 综合征(身材矮小、短指畸形、智力发育障碍和癫痫发作)。我们报告了来自 2 个近亲家庭的另外 3 名患者,他们患有严重/中度智力障碍、身材矮小、短指畸形和畸形。外显子组测序显示 PRMT7 中有 2 个新的纯合突变。我们的发现扩展了与 SBIDDS 综合征相关的纯合 PRMT7 突变的临床和分子谱,显示突变类型与表型严重程度之间可能存在相关性。

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