Nasrin Mansouri, Parichehr Darabi, Masoumeh Favaedi, Hanieh Faizmahdavi, Soheila Nankali, Marjan Assefi, Alireza Sharafshah, Vahid Omarmeli
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引用次数: 0
摘要
视网膜色素变性(RP)是最常见的遗传性视网膜变性疾病,已引起临床和产前关注。考虑到近亲结婚在临床上的重要性,这种类型的妊娠发生新突变的风险很高,也增加了产前诊断(PND)的重要性。2021 年,一名 36 岁的妇女因 PND 转诊到克尔曼沙赫的一家基因实验室,通过全外显子组测序(WES)对其进行了体外分析。该妇女为近亲结婚,并怀有一对双胞胎(一男一女)。为了找到突变,还对她的丈夫和两个胎儿进行了突变确认检测。此外,还利用 SWISS-MODEL、ProSA、Molprobity、Swiss-Pdb Viewer 和 ERRAT 进行了硅学分析。WES 分析显示,这名 36 岁孕妇的 RP2 基因有一个新的突变(外显子 2:c. 359G>C:p.R120P)。在其丈夫和双胞胎体内发现的突变显示了蛋白质构象的变化。进一步的建模和验证评估显示,在同源蛋白的第 120 个残基位点,Arg 被 Pro 取代。我们的报告首次介绍了伊朗一个家族中与严重 RP 症状相关的 RP2 基因错义突变,该突变具有 X 连锁隐性遗传模式。这些发现可能为在遗传咨询和 PND 中更好地诊断 RP 铺平了道路。
A Novel Arg120Pro Mutation in the RP2 Gene in an Iranian Family with X-linked Retinitis Pigmentosa: A Case Report.
As the most common type of inherited retinal degenerative disease, retinitis pigmentosa (RP) has taken clinical and prenatal attention. Considering the clinical importance of consanguineous marriages, new mutations in this type of pregnancy have a high risk and increase the importance of Prenatal Diagnosis (PND). In vitro analysis was done through Whole Exome Sequencing (WES) for a 36-year-old woman who was referred to a genetic laboratory in Kermanshah in 2021 for PND. The woman had consanguineous marriage and was pregnant with twins (a boy and a girl). Mutation confirmation tests were also performed on her husband and both fetuses to find mutations. Moreover, in silico analyses were performed by SWISS-MODEL, ProSA, Molprobity, Swiss-Pdb Viewer, and ERRAT. The WES analysis showed a novel mutation of the RP2 gene (exon2:c. 359G>C: p.R120P) in the 36-year-old pregnant woman. Mutations identified in her husband and her twins revealed changes in protein conformations. Further modeling and validation evaluations showed the replacement of Arg by Pro at the 120th residue site of the cognate protein. For the first time, our report introduced a novel missense mutation in the RP2 gene associated with severe signs of RP in an Iranian family based on an X-linked recessive pattern of genetic inheritance. These findings may pave the way for a better diagnosis of RP in genetic counseling and PND.
期刊介绍:
The Iranian Journal of Medical Sciences (IJMS) is an international quarterly biomedical publication, which is sponsored by Shiraz University of Medical Sciences. The IJMS intends to provide a scientific medium of communication for researchers throughout the globe. The journal welcomes original clinical articles as well as clinically oriented basic science research experiences on prevalent diseases in the region and analysis of various regional problems.