Supplementary Material for: A Novel Aberrant Splice Site Mutation in <b><i>RAB23</i></b> Leads to an Eight Nucleotide Deletion in the mRNA and Is Responsible for Carpenter Syndrome in a Consanguineous Emirati Family

Carpenter syndrome is caused by mutations in the <i>RAB23</i> gene that encodes a small GTPase of the Rab subfamily of proteins. Rab proteins are known to be involved in the regulation of cellular trafficking and signal transduction. Currently, only few mutations in <i>RAB23 </i>have been reported in patients with Carpenter syndrome. In this paper, we report the clinical features, molecular and functional analysis of 2 children from an Emirati consanguineous family with this syndrome. The affected children exhibit the typical features including craniosynostosis, typical facial appearance, polysyndactyly, and obesity. Molecular analysis of the <i>RAB23</i> gene revealed a homozygous mutation affecting the first nucleotide of the acceptor splice site of exon 5 (c.482-1G&gt;A). This mutation affects the authentic mRNA splicing and activates a cryptic acceptor site within exon 5. Thus, the erroneous splicing results in an eight nucleotide deletion, followed by a frameshift and premature termination codon at position 161 (p.V161fsX3). Due to the loss of the C-terminally prenylatable cysteine residue, the truncated protein will probably fail to associate with the target cellular membranes due to the absence of the necessary lipid modification. The p.V161fsX3 extends the spectrum of <i>RAB23</i> mutations and points to the crucial role of prenylation in the pathogenesis of Carpenter syndrome within this family.卡彭特综合征（Carpenter syndrome）由编码Rab蛋白亚家族小GTP酶的RAB23基因（RAB23）发生突变所引发。已知Rab蛋白参与调控细胞运输与信号转导过程。目前，仅少数卡彭特综合征患者被报道携带RAB23基因突变。本研究报道了一个阿联酋近亲通婚家族中2名受累患儿的临床特征、分子及功能分析结果。该两名患儿表现出该病的典型表型，包括颅缝早闭、特征性面容、多指（趾）并指（趾）症以及肥胖。对RAB23基因的分子分析显示，存在一处纯合突变，该突变影响外显子5剪接受体位点的首个核苷酸（c.482-1G>A）。该突变可干扰正常的mRNA剪接，并激活外显子5内的隐蔽剪接受体位点，由此导致的错误剪接会造成8个核苷酸的缺失，进而引发移码突变，并在第161位氨基酸处产生提前终止密码子（p.V161fsX3）。由于该突变导致C端可异戊二烯化修饰的半胱氨酸残基丢失，截短后的蛋白因缺乏必要的脂质修饰，大概率无法靶向结合细胞膜。此次发现的p.V161fsX3突变拓展了RAB23基因突变谱，同时也证实了异戊二烯化修饰在该家族卡彭特综合征发病机制中的关键作用。

搜集汇总

背景与挑战

背景概述

该数据集是关于Carpenter综合征的补充材料，重点研究了一个阿联酋近亲家庭中RAB23基因的新型剪接位点突变（c.482-1G>A），该突变导致mRNA出现八核苷酸缺失，并可能通过影响蛋白质预酰化机制引发疾病。数据集包括临床特征分析、分子功能数据，以及相关文件，旨在扩展对RAB23基因突变谱和Carpenter综合征病理机制的理解。