Bagabir Hala Abubaker, Abdulkareem Angham Abdulrhman, Muthaffar Osama Yousef, Shirah Bader H, Naseer Muhammad Imran
Hala Abubaker Bagabir Physiology Department, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.
Angham Abdulrhman Abdulkareem Center of Excellence in Genomic Medicine Research, Faculty of Science, Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia.
Pak J Med Sci. 2024 Nov;40(10):2243-2250. doi: 10.12669/pjms.40.10.10474.
BACKGROUND & OBJECTIVE: Autosomal recessive cerebellar ataxias (ARCA) are rare heterogenous neurodegenerative disorders characterized by degeneration of the cerebellum and spinal cord with an early onset before the age of 20 years. PMPCA (MIM: 613036), is a key enzyme in mitochondrial protein processing which is critical for cell survival and growth. Our objective was to investigate Peptidase, Mitochondrial Processing Subunit Alpha (PMPCA) mutations linked with Spinocerebellar ataxia, autosomal recessive 2 (SCAR2).
In the current study, Whole Exome Sequencing (WES) was done followed by Sanger sequencing for the validation of the WES results.
WES results identified a novel homozygous variant, NM_015160.2: c.802C>T p.(Arg268Trp) in gene. Mutation in this gene leads to progressive cerebellar ataxia with fine motor skills difficulties, intentional tremors, slow slurred speech and learning difficulties in a 12-year-old Saudi patient. WES results were further validated by Sanger sequencing technique.
Identified phenotype in our case was similar as previously described for SCAR2 related conditions. To our knowledge, this is the first reported mutation in gene leading to SCAR2 in Saudi Arabia. These findings will enrich the scarce literature, further provide a new insight on the role of gene-related disorders leading to SCAR2 and expand the disease concept. In addition, this will help to establish a database for the disease and its causative factors will further help in controlling diseases resulting from consanguinity in Saudi population.
常染色体隐性遗传性小脑共济失调（ARCA）是一种罕见的异质性神经退行性疾病，其特征为小脑和脊髓变性，发病早于20岁。PMPCA（MIM: 613036）是线粒体蛋白加工中的关键酶，对细胞存活和生长至关重要。我们的目的是研究与常染色体隐性遗传性脊髓小脑共济失调2型（SCAR2）相关的线粒体加工肽酶亚基α（PMPCA）突变。
在本研究中，先进行了全外显子组测序（WES），随后进行桑格测序以验证WES结果。
WES结果在该基因中鉴定出一个新的纯合变异，NM_015160.2: c.802C>T p.(Arg268Trp)。该基因的突变导致一名12岁沙特患者出现进行性小脑共济失调，并伴有精细运动技能困难、意向性震颤、缓慢含糊的言语和学习困难。WES结果通过桑格测序技术进一步得到验证。
我们病例中所确定的表型与先前描述的与SCAR2相关的病症相似。据我们所知，这是沙特阿拉伯首次报道的该基因导致SCAR2的突变。这些发现将丰富稀缺的文献资料，进一步为导致SCAR2的该基因相关疾病的作用提供新的见解，并扩展疾病概念。此外，这将有助于建立该疾病的数据库，其致病因素将进一步有助于控制沙特人群中因近亲结婚导致的疾病。
