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Compound heterozygous mutations in CFTR causing congenital bilateral absence of the vas deferens in a Chinese pedigree.
Li, Lingyi; Qu, Xiaowei; Cui, Chenchen; Feng, Ke; Xia, Yanqing; Wan, Feng; Ge, Hengtao; Fang, Yinghong; Zhang, Cuilian; Guo, Haibin.
Afiliação
  • Li L; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • Qu X; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • Cui C; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • Feng K; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • Xia Y; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • Wan F; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • Ge H; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • Fang Y; Department of Reproductive Medicine Center, Zhengzhou University People's Hospital, Zhengzhou, Henan, China.
  • Zhang C; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • Guo H; Department of Reproductive Medicine Center, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Mol Genet Genomic Med ; 12(1): e2364, 2024 Jan.
Article em En | MEDLINE | ID: mdl-38284450
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose Cística / Doenças Urogenitais Masculinas / Infertilidade Masculina Tipo de estudo: Prognostic_studies Limite: Humans / Male País/Região como assunto: Asia Idioma: En Revista: Mol Genet Genomic Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose Cística / Doenças Urogenitais Masculinas / Infertilidade Masculina Tipo de estudo: Prognostic_studies Limite: Humans / Male País/Região como assunto: Asia Idioma: En Revista: Mol Genet Genomic Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China