PhD Scientific Days 2020

Clinical Medicine III. Posters

Penetrance of the CFTR 5T Allele in Congenital Bilateral Absence of the Vas Deferens

Előadó neve

Dr. Dániel, Seidl

Előadó munkahelye

MTA-SE Lendület Nephrogenetic Laboratory, Hungarian Academy of Sciences; First Department of Pediatrics, Semmelweis University

Előadó telefonszáma

+36207700805

Előadó e-mail címe

seidl.daniel@med.semmelweis-univ.hu

Az előadás címe

Penetrance of the CFTR 5T Allele in Congenital Bilateral Absence of the Vas Deferens

Szerző(k) neve és munkahelye

Dániel Seidl1,2, Ágnes Mikó1,2, Ambrus Kaposi1, Kálmán Tory1,2
1MTA-SE Lendület Nephrogenetic Laboratory, Hungarian Academy of Sciences
2First Department of Pediatrics, Semmelweis University, 1083, Budapest, Hungary

Szekció

Clinical Medicine III. Posters

Language of the presentation

Hungarian

Section, first choice

Clinical Medicine

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Congenital bilateral absence of the vas deferens (CBAVD) is responsible for 2% of male infertility. One third (25-40%) of patients with CBAVD are compound heterozygous for the CFTR 5T (c.1210-7_1210-6delTT) variant and another variant in trans. The 5T allele, with a MAF of 3% in the general European population, causes the loss of exon 10 in 95% of mRNA.

Aims: Using a formerly developed population-genetic algorithm we aimed to assign the penetrance of the 5T variant.

Method: We collected phenotype and genotype data from 3279 patients with biallelic CFTR mutations from PubMed. The penetrance (P) of the 5T variant was calculated by comparing its allele count (AC) to the AC of the loss-of-function (LOF) variants in the European non-Finnish patient population and in the gnomAD as P=(AC5T/ACLOF)patient/(AC5T/ACLOF)gnomAD, tested by Fisher’s exact test.

Results: We found the 5T allele in 339/3279 (10.34%) patients, trans-associated to LOF mutations in 187/635 (29.3%) of the patients with CBAVD. None of the compound heterozygous patients with the 5T allele (without other variant in cis) developed CF. We found the penetrance of the 5T variant to be 4.3% (p=5x10-389).

Conclusions: According to our penetrance estimation, for a couple with heterozygous CFTR 5T allele in one parent and a LOF variant in another, the risk of a son being affected by CBAVD is 1% (25% x 4.3%).

Supported by the ÚNKP-19-3-II New National Excellence Program of the Ministry for Innovation and Technology.

Additional Information

Supervisor: Kálmán Tory
E-mail address: tory.kalman@med.semmelweis-univ.hu

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4771

Start

12:28

End

12:31

Authors (legacy)

Dániel Seidl1,2, Ágnes Mikó1,2, Ambrus Kaposi1, Kálmán Tory1,2
1MTA-SE Lendület Nephrogenetic Laboratory, Hungarian Academy of Sciences
2First Department of Pediatrics, Semmelweis University, 1083, Budapest, Hungary