Identification of Three Novel Mutations in the FANCA, FANCC, and ITGA2B Genes by Whole Exome Sequencing

Samira Negahdari; Mina Zamani; Tahereh Seifi; Sahar Sedighzadeh; Neda Mazaheri; Jawaher Zeighami; Alireza Sedaghat; Alihossein Saberi; Mohammad Hamid; Bijan Keikhaei; Ramin Radpour; Gholamreza Shariati; Hamid Galehdari

doi:10.4103/ijpvm.IJPVM_462_19

Identification of Three Novel Mutations in the FANCA, FANCC, and ITGA2B Genes by Whole Exome Sequencing

Int J Prev Med. 2020 Aug 6:11:117. doi: 10.4103/ijpvm.IJPVM_462_19. eCollection 2020.

Authors

Samira Negahdari¹, Mina Zamani^{1

2}, Tahereh Seifi^{1

2}, Sahar Sedighzadeh^{1

2}, Neda Mazaheri¹, Jawaher Zeighami¹, Alireza Sedaghat^{1

3}, Alihossein Saberi^{1

4}, Mohammad Hamid^{1

5}, Bijan Keikhaei⁶, Ramin Radpour^{7

8}, Gholamreza Shariati^{1

4}, Hamid Galehdari⁶

Affiliations

¹ Narges Genetics Diagnostic Laboratory, Ahvaz, Iran.
² Department of Genetics, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
³ Health Research Institute, Diabetes Research Center, Ahvaz Jundishapur Universityof medical Sciences, Ahvaz, Iran.
⁴ Department of Genetics, Ahvaz Jundishapur University of medical Sciences, Ahvaz, Iran.
⁵ Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
⁶ Health Research Institute, Research Centre of Thalassemia and Hemoglobinopathies, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁷ Tumor Immunology, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
⁸ Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Abstract

Background: Various blood diseases are caused by mutations in the FANCA, FANCC, and ITGA2B genes. Exome sequencing is a suitable method for identifying single-gene disease and genetic heterogeneity complaints.

Methods: Among families who were referred to Narges Genetic and PND Laboratory in 2015-2017, five families with a history of blood diseases were analyzed using the whole exome sequencing (WES) method.

Results: We detected two novel mutations (c.190-2A>G and c.2840C>G) in the FANCA gene, c. 1429dupA mutation in the FANCC gene, and c.1392A>G mutation in the ITGA2B gene. The prediction of variant pathogenicity has been done using bioinformatics tools such as Mutation taster PhD-SNP and polyphen2 and were confirmed by Sanger sequencing.

Conclusions: WES could be as a precise tool for identifying the pathologic variants in affected patient and heterozygous carriers among families. This highly successful technique will remain at the forefront of platelet and blood genomic research.

Keywords: Blood platelets; DNA; Fanconi anemia; congenital abnormalities; sequence analysis.