Novel DNAAF6 Variants Identified by Whole-exome Sequencing Cause Male Infertility and Primary Ciliary Dyskinesia

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2020 Mar 15

PMID 32170493

Citations 8

Authors

Ying Wang

Chaofeng Tu

Hongchuan Nie

Lanlan Meng

Dongyan Li

Weili Wang

Huan Zhang

Guangxiu Lu

Ge Lin

Yue-Qiu Tan

Juan Du

Affiliations

Soon will be listed here.

Abstract

Purpose: To identify the genetic cause of patients with primary ciliary dyskinesia (PCD) and male infertility from two unrelated Han Chinese families.

Methods: We conducted whole-exome sequencing of three individuals with PCD and male infertility from two unrelated Chinese families, and performed a targeted look-up for DNAAF6 variants in our previously reported cohort of 442 individuals (219 with isolated oligoasthenospermia and 223 fertile controls). Ultrastructural and immunostaining analyses of patients' spermatozoa were performed. The pathogenicity of the variants was validated using patient's spermatozoa and HEK293T cells. Intracytoplasmic sperm injection (ICSI) treatment was conducted in two patients.

Results: We identified one novel hemizygous frameshift variant (NM_173494, c.319_329del: p.R107fs) of DNAAF6 gene (previously named PIH1D3) in family 1 and one novel hemizygous missense variant (c.290G>T: p.G97V) in family 2. No hemizygous deleterious variants in DNAAF6 were detected in the control cohort of 442 individuals. Ultrastructural and immunostaining analyses of patients' spermatozoa showed the absence of outer and inner dynein arms in sperm flagella. Both variants were proven to lead to DNAAF6 protein degradation in HEK293T cells. Both patients carrying DNAAF6 variants underwent one ICSI cycle and delivered one healthy child each.

Conclusion: We identified novel DNAAF6 variants causing male infertility and PCD in Han Chinese patients. This finding extended the spectrum of variants in DNAAF6 and revealed new light on the impact of DNAAF6 variants in sperm flagella.

Citing Articles

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A novel homozygous mutation of CFAP300 identified in a Chinese patient with primary ciliary dyskinesia and infertility.

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Newman L, Chopra J, Dossett C, Shepherd E, Bercusson A, Carroll M Hum Reprod Update. 2023; 29(3):347-367.

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Peng B, Gao Y, Xie J, He X, Wang C, Xu J Orphanet J Rare Dis. 2022; 17(1):283.

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