Novel DNAAF6 variants identified by whole-exome sequencing cause male infertility and primary ciliary dyskinesia
Novel DNAAF6 variants identified by whole-exome sequencing cause male infertility and primary ciliary dyskinesia
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全外显子组测序鉴定出的新 DNAAF6 变异导致男性不育和原发性纤毛运动障碍
DOI：
10.1007/s10815-020-01735-4
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发表时间：
2020-03
影响因子：
3.1
通讯作者：
Du Juan
中科院分区：
文献类型：
--
作者：
Wang Ying;Tu Chaofeng;Nie Hongchuan;Meng Lanlan;Li Dongyan;Wang Weili;Zhang Huan;Lu Guangxiu;Lin Ge;Tan Yue-Qiu;Du Juan
目的探讨原发性睫状体运动障碍（PCD）和男性不育症的遗传病因。我们对来自两个不相关的中国家庭的三名PCD和男性不育患者进行了全外显子组测序，并在我们先前报道的442名患者（219名孤立的寡弱精子症患者和223名生育对照）中进行了DNAAF6变体的靶向查找。对患者的精子进行超微结构和免疫染色分析。使用患者的精子和HEK293 T细胞验证变体的致病性。对2例患者进行了卵胞浆内单精子注射（ICSI）治疗。我们在家族1中鉴定了一种新的DNAAF 6基因的半合子移码变体（NM_173494，c.319_329del：p.R107fs）（以前称为PIH1D3），在家族2中鉴定了一种新的半合子错义变体（c.290G T：p.G97V）。在442个个体的对照组中没有检测到DNAAF6的半合子有害变体。患者精子的超微结构和免疫组化分析显示精子鞭毛中缺乏外和内动力蛋白臂。这两种变体都被证明在HEK293T细胞中导致DNAAF6蛋白降解。两名携带DNAAF6变异体的患者均接受了一个ICSI周期，并各分娩了一名健康儿童。我们在中国汉族患者中鉴定了导致男性不育和PCD的新DNAAF6变体。这一发现扩展了DNAAF6变体的范围，并揭示了DNAAF6变体在精子鞭毛中的影响。
To identify the genetic cause of patients with primary ciliary dyskinesia (PCD) and male infertility from two unrelated Han Chinese families. 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. 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. 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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影响因子：
5.8
作者：
Ziętkiewicz E;Nitka B;Voelkel K;Skrzypczak U;Bukowy Z;Rutkiewicz E;Humińska K;Przystałowska H;Pogorzelski A;Witt M
通讯作者：
Witt M
DOI：
--
发表时间：
2012-10
期刊：
EJIFCC
影响因子：
--
作者：
J. Sánchez-Álvarez;Ruth Cano-Corres;X. Fuentes-Arderiu
通讯作者：
J. Sánchez-Álvarez;Ruth Cano-Corres;X. Fuentes-Arderiu
影响因子：
7.7
作者：
G. Mali;P. Yeyati;S. Mizuno;M. Keighren;P. zur Lage;A. García-Muñoz;A. Shimada;H. Takeda;F. Edlich;Satoru Takahashi;A. von Kriegsheim;A. Jarman;P. Mill
通讯作者：
G. Mali;P. Yeyati;S. Mizuno;M. Keighren;P. zur Lage;A. García-Muñoz;A. Shimada;H. Takeda;F. Edlich;Satoru Takahashi;A. von Kriegsheim;A. Jarman;P. Mill
影响因子：
9.8
作者：
Fassad, Mahmoud R.;Shoemark, Amelia;Mitchison, Hannah M.
通讯作者：
Mitchison, Hannah M.
影响因子：
9.8
作者：
Hoeben, Inga M.;Hjeij, Rim;Omran, Heymut
通讯作者：
Omran, Heymut