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المؤلفIbrahim, Ali Zaki
المؤلفThirumal Kumar, D
المؤلفAbunada, Taghreed
المؤلفYounes, Salma
المؤلفGeorge Priya Doss, C
المؤلفZaki, Osama K
المؤلفZayed, Hatem
تاريخ الإتاحة2020-10-28T09:19:22Z
تاريخ النشر2020-12-01
اسم المنشورMolecular Genetics and Metabolism Reports
المعرّفhttp://dx.doi.org/10.1016/j.ymgmr.2020.100645
الاقتباسIbrahima, 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
المعرّف100645
معرّف المصادر الموحدhttp://hdl.handle.net/10576/16823
الملخصPropionic 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.
اللغةen
الناشرElsevier
الموضوعComputational analysis
Genotype-phenotype correlation
Next-generation sequencing
PCCA gene
Propionic acidemia (PA)
العنوانInvestigating the structural impacts of a novel missense variant identified with whole exome sequencing in an Egyptian patient with propionic acidemia
النوعArticle
رقم المجلد25
dc.accessType Open Access


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