A novel nonsense mutation in NPR2 gene causing Acromesomelic dysplasia, type Maroteaux in a consanguineous family in Southern Punjab (Pakistan)
| العنوان: | A novel nonsense mutation in NPR2 gene causing Acromesomelic dysplasia, type Maroteaux in a consanguineous family in Southern Punjab (Pakistan) |
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| المؤلفون: | Muhammad Latif, Saima Mustafa, Muhammad Faisal, Zafrin Akhtar, Furhan Iqbal, Mubashir Hassan |
| المصدر: | Genes & Genomics |
| بيانات النشر: | Springer Singapore, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Sanger sequencing, Nonsense mutation, Western blot, Dwarfism, 030105 genetics & heredity, Biology, Osteochondrodysplasias, Biochemistry, Polymerase Chain Reaction, AMDM, 03 medical and health sciences, Exon, symbols.namesake, Consanguinity, Exome Sequencing, Genetics, medicine, Escherichia coli, Humans, Pakistan, Molecular Biology, Gene, Exome sequencing, medicine.disease, NPR2, 3D protein structure, Pedigree, 030104 developmental biology, HEK293 Cells, Phenotype, Dysplasia, Codon, Nonsense, Mutation (genetic algorithm), symbols, WES, Female, Receptors, Atrial Natriuretic Factor, Research Article |
| الوصف: | Background Acromesomelic dysplasia, type Maroteaux (AMDM) is a rare skeletal dysplasia following autosomal recessive mode of inheritance and characterized by abnormal growth plates, short and abnormal bones in the extremities and spine. Objective Present study was designed to report the molecular basis of AMDM in enrolled consanguineous family from Pakistan. Methods A consanguineous family from Vehari District in Pakistan having multiple siblings suffering from AMDM was enrolled in present study. Whole exome sequencing (WES) approach was adopted to identify causative agent of AMDM. Human full length NPR2 gene and sequence with nonsense mutation was amplified by using Myc-tagged pXN vector and transformed in E. coli DH5α cells to confirm mutation. SDS-PAGE and Western blotting were done to confirm the production of truncated protein. Computational three dimensional structure generation through homology modeling approach was done to compare protein structure between patients and controls. Results WES reveled a nonsense mutation (c.613 C>T, p.R205X) in exon 1 of NPR2 gene leading to premature termination codon in mRNA of NPR2 gene resulting in a truncated protein with 204 amino acid residues that was confirmed by SDS-PAGE and Western blotting. Sanger sequencing confirmed that mutation in all subjects and mutation followed Mendalian pattern of inheritance. Multiple sequence alignment by ClustalW revealed that mutated domain of NPR2 is conserved region. Proetin structure comparison revealed a significant structural part of NPR2 was missing in truncated protein as compared to control. Conclusion We are reporting that a novel nonsense mutation (c.613 C>T, p.R205X) in exon 1 of NPR2 gene is causing AMDM in a consanguineous Pakistani family. |
| اللغة: | English |
| تدمد: | 2092-9293 1976-9571 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99a3ad70eaf045a3cf2a0f72dd2d343eTest http://europepmc.org/articles/PMC7374443Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....99a3ad70eaf045a3cf2a0f72dd2d343e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20929293 19769571 |
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