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Published in: Journal of Assisted Reproduction and Genetics 4/2020

01-04-2020 | Infertility | Genetics

Novel DNAAF6 variants identified by whole-exome sequencing cause male infertility and primary ciliary dyskinesia

Authors: Ying Wang, Chaofeng Tu, Hongchuan Nie, Lanlan Meng, Dongyan Li, Weili Wang, Huan Zhang, Guangxiu Lu, Ge Lin, Yue-Qiu Tan, Juan Du

Published in: Journal of Assisted Reproduction and Genetics | Issue 4/2020

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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.
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Metadata
Title
Novel DNAAF6 variants identified by whole-exome sequencing cause male infertility and primary ciliary dyskinesia
Authors
Ying Wang
Chaofeng Tu
Hongchuan Nie
Lanlan Meng
Dongyan Li
Weili Wang
Huan Zhang
Guangxiu Lu
Ge Lin
Yue-Qiu Tan
Juan Du
Publication date
01-04-2020
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 4/2020
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-020-01735-4

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