https://doi.org/10.4081/aiua.2024.12464

CFTR Exon 10 deleterious mutations in patients with congenital bilateral absence of vas deferens in a cohort of Pakistani patients

Vol. 96 No. 3 (2024)
Submitted: March 16, 2024
Accepted: April 5, 2024
Published: October 2, 2024
CFTR, CBAVD, Mutation Analysis, Infertility, andrology
Abstract Views: 228
PDF: 64
Supplementary: 43
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Authors

Khush Bakhat
https://orcid.org/0009-0000-0797-069X
KAM School of Life Science, Forman Christian College, (A Chartered University), Lahore, Pakistan.
Irsa Mateen
School of Biochemistry, Minhaj University, Lahore, Pakistan.
Hina Saif
https://orcid.org/0009-0006-3635-0004
Department of Emerging Allied Health Technologies, University of Lahore, Pakistan.
Kanwal Anwar
https://orcid.org/0009-0006-3974-6282
KAM School of Life Science, Forman Christian College, (A Chartered University), Lahore, Pakistan.
Sadaf Sarfraz
https://orcid.org/0000-0002-9474-585X
KAM School of Life Science, Forman Christian College, (A Chartered University), Lahore, Pakistan.
Sheza Javaid
https://orcid.org/0009-0002-7522-9793
KAM School of Life Science, Forman Christian College, (A Chartered University), Lahore, Pakistan.
Khaleeq ur Rehman
https://orcid.org/0000-0001-8786-380X
Department of Urology, Fatima Memorial Hospital College of Medicine & Dentistry, Lahore, Pakistan.
Adnan Arshad
https://orcid.org/0000-0001-6653-9218
KAM School of Life Science, Forman Christian College, (A Chartered University), Lahore, Pakistan.
Muhammad Mustafa
muhammadmustafa@fccollege.edu.pk
https://orcid.org/0000-0002-8714-5311
KAM School of Life Science, Forman Christian College, (A Chartered University), Lahore, Pakistan.

Congenital bilateral absence of vas deferens (CBAVD) is a urological syndrome of Wolffian ducts and is responsible for male infertility and obstructive azoospermia. This study is designed to explore the integrity of exon 10 of CFTR and its role in male infertility in a cohort of CBVAD patients in Pakistan. Genomic DNA was extracted from 17 male patients with CBAVD having clinical symptoms, and 10 healthy controls via phenol-chloroform method. Exon 10 of the CFTR gene was amplified, using PCR with specific primers and DNA screening was done by Sanger sequencing. Sequencing results were analyzed using freeware Serial Cloner, SnapGene, BioEdit and FinchTV. Furthermore, bioinformatics tools were used to analyze the mutations and their impact on the protein function and stability. We have identified 4 mutations on exon 10 of CFTR in 6 out of 17 patients. Two of the mutations were missense variants V456A, K464E, and the other two were silent mutations G437G, S431S. The identified variant V456A was present in 4 of the studied patients. Whereas, the presence of K464E in our patients further weighs on the crucial importance for its strategic location to influence the gene function at post-transcriptional and protein level. Furthermore, Polyphen-2 and SIFT analyze the mutations as harmful and deleterious. The recurrence of V456A and tactically conserved locality of K464E are evidence of their potential role in CBAVD patients and in male infertility. The data can contribute in developing genetic testing and treatment of CBAVD.

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How to Cite

Bakhat , K., Mateen, I., Saif, H., Anwar, K., Sarfraz, S., Javaid, S., ur Rehman , K., Arshad, A., & Mustafa, M. (2024). CFTR Exon 10 deleterious mutations in patients with congenital bilateral absence of vas deferens in a cohort of Pakistani patients. Archivio Italiano Di Urologia E Andrologia, 96(3). https://doi.org/10.4081/aiua.2024.12464
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