Investigating the structural impacts of a novel missense variant identified with whole exome sequencing in an Egyptian patient with propionic acidemia
المؤلف | Ibrahim, Ali Zaki |
المؤلف | Thirumal Kumar, D |
المؤلف | Abunada, Taghreed |
المؤلف | Younes, Salma |
المؤلف | George Priya Doss, C |
المؤلف | Zaki, Osama K |
المؤلف | Zayed, Hatem |
تاريخ الإتاحة | 2020-10-28T09:19:22Z |
تاريخ النشر | 2020-12-01 |
اسم المنشور | Molecular Genetics and Metabolism Reports |
المعرّف | http://dx.doi.org/10.1016/j.ymgmr.2020.100645 |
الاقتباس | Ibrahima, Ali Zaki et. al. Investigating the structural impacts of a novel missense variant identified with whole exome sequencing in an Egyptian patient with propionic acidemia. Molecular Genetics and Metabolism Reports. Molecular Genetics and Metabolism Reports. Volume 25, December 2020, 100645 |
المعرّف | 100645 |
الملخص | Propionic Acidemia (PA) is an inborn error of metabolism caused by variants in the or genes, leading to mitochondrial accumulation of propionyl-CoA and its by-products. Here, we report a 2 year-old Egyptian boy with PA who was born to consanguineous parents. Biochemical analysis was performed using tandem mass spectrometry (MS/MS) on the patient's dried blood spots (DBS) followed by urine examination of amino acids using gas chromatography/mass spectrometry (GC/MS). Molecular genetic analysis was carried out using whole-exome sequencing (WES). The gene sequencing revealed a novel homozygous missense variant affecting the locus (chr13:100962160) of exon 16 of the gene, resulting in the substitution of the amino acid arginine with proline at site 476 (p.Arg476Pro). Computational analysis revealed that the novel variant might be pathogenic and attributed to decrease the stability and also has an effect on the biotin carboxylase c-terminal domain of the propionyl carboxylase enzyme. The physicochemical properties analysis using NCBI amino acid explorer study revealed restrictions in the side chain and loss of hydrogen bonds due to the variant. On the structural level, the loss of beta-sheet was observed due to the variant proline, which has further led to the loss of surrounding interactions. This loss of beta-sheet and the surrounding interactions might serve the purpose of the structural stability changes. The current study demonstrates that a combination of whole-exome sequencing (WES) and computational analysis are potent tools for validation of diagnosis and classification of disease-causing variants. |
اللغة | en |
الناشر | Elsevier |
الموضوع | Computational analysis Genotype-phenotype correlation Next-generation sequencing PCCA gene Propionic acidemia (PA) |
النوع | Article |
رقم المجلد | 25 |
تحقق من خيارات الوصول
الملفات في هذه التسجيلة
هذه التسجيلة تظهر في المجموعات التالية
-
العلوم الحيوية الطبية [723 items ]