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Journal of Assisted Reproduction and Genetics

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01-12-2019 | Infertility | Genetics

A rare frameshift variant in trans with the IVS9-5T allele of CFTR in a Chinese pedigree with congenital aplasia of vas deferens

Authors: Bin Ge, Mingzhe Zhang, Ruyi Wang, Dejing Wang, Tengyan Li, Hongjun Li, Binbin Wang

Published in: Journal of Assisted Reproduction and Genetics | Issue 12/2019

Abstract

Purpose

Congenital aplasia of vas deferens (CAVD) is an atypical form of cystic fibrosis (CF) and causes obstructive azoospermia and male infertility. Compound heterozygous variants of CFTR are the main cause of CAVD. However, most evidence comes from genetic screening of sporadic cases and little is from pedigree analysis. In this study, we performed analysis in a Chinese pedigree with two CAVD patients in order to determine the genetic cause of this familial disorder.

Methods

In the present study, we performed whole-exome sequencing and co-segregation analysis in a Chinese pedigree involving two patients diagnosed with CAVD.

Results

We identified a rare frameshift variant (NM_000492.3: c.50dupT;p.S18Qfs*27) and a frequent CBAVD-causing variant (IVS9-TG13-5T) in both patients. The frameshift variant introduced a premature termination codon and was not found in any public databases or reported in the literature. Co-segregation analysis confirmed these two variants were in compound heterozygous state. The other male members, who harbored the frameshift variant and benign IVS9-7T allele, did not have any typical clinical manifestations of CF or CAVD.

Conclusion

Our findings may broaden the mutation spectrum of CFTR in CAVD patients and provide more familial evidence that the combination of a mild variant and a severe variant in trans of CFTR can cause vas deferens malformation.

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Title: A rare frameshift variant in trans with the IVS9-5T allele of CFTR in a Chinese pedigree with congenital aplasia of vas deferens
Authors: Bin Ge
Mingzhe Zhang
Ruyi Wang
Dejing Wang
Tengyan Li
Hongjun Li
Binbin Wang
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Infertility
Cystic Fibrosis
Infertility
Cystic Fibrosis
Published in: Journal of Assisted Reproduction and Genetics / Issue 12/2019
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-019-01617-4

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A rare frameshift variant in trans with the IVS9-5T allele of CFTR in a Chinese pedigree with congenital aplasia of vas deferens

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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