Compound Heterozygous Mutations in CFTR Causing Congenital Bilateral Absence of the Vas Deferens in a Chinese Pedigree

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2024 Jan 29

PMID 38284450

Authors

Lingyi Li

Xiaowei Qu

Chenchen Cui

Ke Feng

Yanqing Xia

Feng Wan

Hengtao Ge

Yinghong Fang

Cuilian Zhang

Haibin Guo

Affiliations

Soon will be listed here.

Abstract

Background: Cystic fibrosis (CF) is an autosomal recessive disorder rarely found in Asian populations. Most males with CF are infertile because of obstructive azoospermia (OA) caused by congenital bilateral absence of the vas deferens (CBAVD). Compound heterozygous mutations of cystic fibrosis transmembrane conductance regulator (CFTR) are among the most common pathogenic factors in CBAVD. However, few genealogical analyses have been performed.

Methods: In this study, whole-exome sequencing and cosegregation analysis were performed in a Chinese pedigree involving two siblings with CBAVD. Moreover, in vitro gene expressions were used to analyze the pathogenicity of a novel CFTR mutation.

Results: We identified compound heterozygous mutations of CFTR comprising the known disease-causing variant c.1210-11T>G (also known as IVS9-5 T) and c.2144delA;p.q715fs in two siblings with CBAVD. To verify the effects in vitro, we transfected vectors expressing wild-type and mutated CFTR into 293T cells. The results showed that the CFTR protein containing the frameshift mutation (c.2144delA) was 60 kD smaller. With testicular sperm aspiration/intracytoplasmic sperm injection-embryo transfer (TESA/ICSI-ET), both CBAVD patients fathered healthy offspring.

Conclusion: Our study revealed that compound heterozygous mutations of CFTR are involved in CBAVD, expanding the known CFTR gene mutation spectrum of CBAVD patients and providing more evidence that compound heterozygous mutations can cause familial CBAVD.

Citing Articles

Compound heterozygous mutations in CFTR causing congenital bilateral absence of the vas deferens in a Chinese pedigree.

Li L, Qu X, Cui C, Feng K, Xia Y, Wan F Mol Genet Genomic Med. 2024; 12(1):e2364.

PMID: 38284450 PMC: 10795088. DOI: 10.1002/mgg3.2364.

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