Two novel mutations in exon 2 of bone morphogenetic protein (BMP) 15 gene in Pakistani infertile females

Hafiza Faiza; Majida Khan; Muhammad Rafiq; Anoshiya Ali Khan; Nadir Ali Rind; Syed Habib Ahmed Naqvi

doi:10.1016/j.sjbs.2021.05.061

Two novel mutations in exon 2 of bone morphogenetic protein (BMP) 15 gene in Pakistani infertile females

Saudi J Biol Sci. 2021 Sep;28(9):5364-5370. doi: 10.1016/j.sjbs.2021.05.061. Epub 2021 May 29.

Authors

Hafiza Faiza¹, Majida Khan², Muhammad Rafiq¹, Anoshiya Ali Khan¹, Nadir Ali Rind^{1

3}, Syed Habib Ahmed Naqvi¹

Affiliations

¹ Institute of Biotechnology and Genetic Engineering, University of Sindh, Jamshoro, Pakistan.
² Department of Gynecology, Liaquat University of Medical Science, Jamshoro, Pakistan.
³ Department of Genetics & Molecular Biology, SBBU, Shaheed Benazirabad, Pakistan.

Abstract

Objective: To determine the proportion of fertility in Pakistani infertile females and discover if there are considerable connection among BMP15 gene polymorphism, follicle maturation and hormonal regulation in Pakistani infertile females.

Methods: All selected participants were initially examined through follicle-stimulating hormones (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), Prolactin, and Trans-vaginal scan (TVS). BMP15 gene polymorphism among infertile and fertile females was done by extracted Genomic DNA from whole blood. Sanger sequencing was performed for the identification of mutation in exons-intron boundaries of the BMP15 gene. Bioinformatics tools were used to assess the protein structure.

Results: The total five mutations including two novel missense variants of BMP15 in exon 2, whereas three previously reported i.e. two cosmic mutations (c.615delC), (c.584InsG) and one frame shift mutations (c.635delA) were also observed. The first novel mutation was found at (c.1038InsGG) (p.346Gln < Gly) in which the insertion of GG at DNA position 1038 of exon 2 resulting in a substitution of glutamine into glycine at 346th amino acid of BMP15 protein. The second novel variant (c.1049delT) (p. Ser334Pro) was also observed in exon 2 of the BMP15 gene, which substituted serine into proline at 334th amino acid of the BMP15 protein.

Conclusion: It is concluded that there are various missense mutations present in exon 2 of the BMP15 gene of Pakistani infertile females, consequently expected function of protein changes due to change in codons of amino acids. Provean and SIFT suggest the two novel variants as potentially deleterious. Although three other variants were also found in Pakistani infertile females which were previously reported. These mutations may result in early blockage of folliculogenesis and ovaries become streaky. Further research is required to resolve the actual allusion of these variations in the BMP15 gene.

Keywords: BMP15 gene; Infertility; Mutation; Sequencing.