Copy Number Variation Analysis in Turkish Patients with Congenital Bilateral Absence of Vas Deferens

Year 2021, Volume: 5 Issue: 2, 181 - 189, 30.08.2021

Durkadın Demir Ekşi , Elanur Yılmaz Yiğit Akın , Mustafa Faruk Usta Mehmet Murad Başar Semra Kahraman Munire Erman , Özgül M. Alper

https://doi.org/10.30565/medalanya.966940

Abstract

Aim: Congenital Bilateral Absence of the Vas Deferens (CBAVD) is a developmental abnormality that causes infertility in males. According to the literature, up to 88% of CBAVD cases have at least one pathogenic Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) mutation. However, based on our previous data, this rate was 15.90% in Turkish patients with CBAVD. We aimed to identify genomic copy number variations (CNV) and candidate genomic regions which could related to the CBAVD in Turkish population.

Methods: CNV analysis was performed in 19 Turkish CBAVD patients normal karyotypes and a wild type CFTR genotype. We suggested that the DAD1 gene may be a candidate gene related to CBAVD by reviewing online databases and analyzing CNV findings. Sanger sequencing of the DAD1 gene exons was performed in 22 patients.

Results: We identified 11 CNVs that most likely related with the disease in nine of 19 (47.3%) patients. As the most common CNV, 14q11.2 deletions were detected in there (15.79%) of the patients. There was only DAD1 gene in the sharing genomic region of two of the 14q11.2 deletions. No sequence variation was detected in the DAD1 gene of the patients.

Conclusion: The 14q11.2 chromosomal region and the DAD1 gene may be associated with CBAVD. Further studies are needed to indentify the contribution of CNVs and DAD1 gene to CBAVD etiology.

Keywords

copy number variations;, CBAVD,, male infertility;, DAD1,

Supporting Institution

TÜBİTAK

Project Number

SBAG-115S171

Thanks

We are thankful to the patients who participated in the study. We also thank Dr. Lynn P. Chorich for checking the spelling.

Konjenital Bilateral Vas Deferens Yokluğu Olan Türk Hastalarda Genomik Kopya Sayısı Varyasyonları Analizi

Abstract

Amaç: Konjenital Bilateral Vas Deferens Yokluğu (CBAVD), erkeklerde infertiliteye yol açan gelişimsel bir anomalidir. Literatüre göre CBAVD’li olguların %88’e kadarı en az bir Kistik Fibrozis Transmembran Regülatör geni (CFTR) mutasyonuna sahiptir. Ancak, daha önceki verilerimize göre CBAVD’li Türk hastalarda bu oran %15.90’dır. Çalışmamız kapsamında Türk popülasyonundaki CBAVD ile ilişkili olabilecek genomik kopya sayısı varyasyonları (CNV) ve aday genomik bölgelerin tanımlanması amaçlanmıştır.

Yöntemler: Normal karyotipe ve yabanıl tip CFTR genotipine sahip 19 Türk CBAVD’li hastanın CNV analizi gerçekleştirildi. CNV bulgularımızın analizi ve veritabanlarının taranması ile DAD1 geni CBAVD ile ilişkili olabilecek potansiyel aday gen olarak tanımlandı. 22 CBAVD’li hastada da DAD1 geni ekzonlarının dizi analizi Sanger dizileme metoduyla yapıldı.

Bulgular: 19 hastanın dokuzunda (%47.3) hastalıkla ilişkili olabilecek 11 adet CNV saptandı. En sık saptanan CNV olarak 14q11.2 delesyonu, hastaların üçünde (%15.79) belirlendi. 14q11.2 delesyonlarından ikisinin ortak varyant bölgesinde yalnızca DAD1 geni lokalize idi. Dizi analizi ile, hastaların DAD1 geninde herhangi bir dizi varyasyonu saptanmadı.

Sonuç: 14q11.2 kromozomal bölgesi ve DAD1 geni CBAVD ile ilişkili olabilir. CNVlerin ve DAD1 geninin CBAVD etiyolojisine katkısını tanımlamak için ileri çalışmalar gerekmektedir.

Keywords

kopya sayısı varyasyonları, CBAVD, erkek infertilitesi, DAD1

Project Number

SBAG-115S171

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