Primary ciliary dyskinesia (PCD) is a group of genetically and clinically heterogeneous disorders with motile cilia dysfunction. It is clinically characterized by oto-sino-pulmonary diseases and subfertility, and half of the patients have situs inversus (Kartagener syndrome). To identify the genetic cause in a Han-Chinese pedigree, whole-exome sequencing was conducted in the 37-year-old proband, and then, Sanger sequencing was performed on available family members. Minigene splicing assay was applied to verify the impact of the splice-site variant. Compound heterozygous variants including a splice-site variant (c.1974-1G>C, rs1359107415) and a missense variant (c.7787G>A, p.(Arg2596Gln), rs780492669), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified and confirmed as the disease-associated variants of this lineage. The minigene expression in vitro revealed that the c.1974-1G>C variant could cause skipping over exon 12, predicted to result in a truncated protein. This discovery may enlarge the DNAH11 variant spectrum of PCD, promote accurate genetic counselling and contribute to PCD diagnosis.

中文翻译：

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原发性纤毛运动障碍汉族家族中复合杂合 DNAH11 变异体的鉴定

原发性纤毛运动障碍 (PCD) 是一组具有运动纤毛功能障碍的遗传和临床异质性疾病。临床上以耳-中-肺疾病和生育力低下为特征，半数患者有内脏倒置（ Kartagener综合征）。为了确定汉族谱系中的遗传原因，对 37 岁的先证者进行了全外显子组测序，然后对可用的家庭成员进行了 Sanger 测序。应用 Minigene 剪接测定来验证剪接位点变体的影响。在动力蛋白轴丝重链 11 基因 ( DNAH11) 被鉴定并确认为该谱系的疾病相关变体。体外小基因表达表明，c.1974-1G>C 变体可能导致跳过外显子 12，预计会导致截短的蛋白质。这一发现可能会扩大PCD的DNAH11变异谱，促进准确的遗传咨询，并有助于PCD的诊断。