Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Biomed Res Int. 2022 Jun 26;2022:7130555. doi: 10.1155/2022/7130555. eCollection 2022.
Primary ciliary dyskinesia (PCD) is a clinical syndrome characterized by cilia with an abnormal structure or function. Its main clinical manifestations comprise chronic bronchitis, cough, recurrent respiratory infections, situs inversus, and male infertility. Single-gene variants are widely assumed to be the main cause of this rare disease, and more than 40 genes have been described to be associated with its onset. is essential for assembling the inner dynein arms and dynein regulatory complex and is important in cilia motility. variants were reported as a monogenic etiology of PCD.
This study investigated two unrelated Chinese patients diagnosed as PCD. The chest computed tomography scan was performed to identify PCD phenotypes of the two probands. Considering the effect of PCD on male fertility, routine semen analysis, sperm morphology examination, and scanning electron microscopy were performed to assess the semen characteristics of male proband in family 2 (F2 II-1), who had a history of infertility. Subsequently, the peripheral blood samples of probands were collected to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease.
Whole-exome sequencing revealed a homozygous variant in the female proband of family 1 (F1 II-1: c.286C>T:p.Arg96Ter) and two compound heterozygous variants in the male proband of family 2 (F2 II-1: c.732_733del: p.Ala245PhefsTer18; c.2800_2802dup:p.Val934dup). The two probands showed the typical PCD phenotypes, including chronic bronchitis, recurrent respiratory infections, and situs inversus. The male proband also showed oligoasthenoteratospermia with multiple morphological abnormalities of the sperm flagella. Additionally, CCDC39 protein level was significantly lower in the sperm of male proband than in the sperm from normal controls.
We identified a homozygous variant reported previously and two compound heterozygous variants of possibly responsible for PCD pathogenesis, expanding the variant spectrum of Chinese PCD, Kartagener syndrome, and morphological abnormalities of the sperm flagella involving .
原发性纤毛运动障碍（PCD）是一种以纤毛结构或功能异常为特征的临床综合征。其主要临床表现包括慢性支气管炎、咳嗽、反复呼吸道感染、内脏转位和男性不育。单基因变异被广泛认为是这种罕见疾病的主要原因，已有 40 多种基因被描述与该病的发病有关。 对于组装内臂动力蛋白和动力蛋白调节复合物至关重要，在纤毛运动中非常重要。 变体被报道为 PCD 的单基因病因。
本研究调查了两名被诊断为 PCD 的无关中国患者。进行胸部计算机断层扫描以确定两名先证者的 PCD 表型。考虑到 PCD 对男性生育能力的影响，对有不育史的家系 2 （F2 II-1）中的男性先证者进行了常规精液分析、精子形态检查和扫描电子显微镜检查，以评估其精液特征。随后，采集先证者的外周血样进行全外显子组测序（WES），以探讨该疾病的可能遗传原因。
全外显子组测序显示，家系 1 （F1 II-1：c.286C>T：p.Arg96Ter）中的女性先证者存在纯合 变体，家系 2 （F2 II-1：c.732_733del：p.Ala245PhefsTer18；c.2800_2802dup：p.Val934dup）中的男性先证者存在两个复合杂合 变体。这两名先证者均表现出典型的 PCD 表型，包括慢性支气管炎、反复呼吸道感染和内脏转位。男性先证者还表现出少精弱精症，精子鞭毛形态异常多样。此外，与正常对照相比，男性先证者的精子中 CCDC39 蛋白水平显著降低。
我们发现了一个先前报道的纯合变体和两个 可能导致 PCD 发病机制的复合杂合变体，扩大了中国 PCD、卡塔格内综合征和涉及 的精子鞭毛形态异常的变异谱。
