[Genetic analysis of primary ciliary dyskinesia caused by <i>DNAH5</i> splicing site mutations].

<b>Objective:</b> To explore the impact of intron region variation in motor protein axonal heavy chain 5 (<i>DNAH5</i>) gene on its transcriptional splicing, and to retrospectively analyze the phenotypic characteristics of patients with primary ciliary dyskinesia caused by <i>DNAH5</i> mutation in the Chinese population. <b>Methods:</b> Two patients with recurrent respiratory symptoms, pulmonary infections and bronchiectasis were selected as the research subjects. Whole exome sequencing was performed in family members to identify possible genetic causes, and Sanger sequencing was used to validate candidate variants. Minigene splicing variant analysis was used to study the pathogenicity of the splicing site variation. The phenotypic characteristics of patients with primary ciliary dyskinesia caused by different mutation types of the <i>DNAH5</i> gene in chinese population were summarized by literature search and screening. <b>Results:</b> Two patients simultaneously carried paternal <i>DNAH5</i> c.12367C>T (p.His4123Tyr) and c.1731-18A>G mutations and maternal c.1933C>T (p.Gln645*) mutation. According to the guidelines of the American Society of Medical Genetics and Genomics, the <i>DNAH5</i> c.1933C>T (p.Gln645*) mutation was classified as pathogenic (PVSl+PM2_Supporting+PP4), and c.1731-18A>G mutation was also classified as pathogenic (PVSl+PM2_Supporting+PM3_Supporting+PP4). <i>DNAH5</i> c.12367C>T mutation was classified as likely benign. Among the major phenotypes of patients with <i>DNAH5</i> mutation in Chinese population, cough, chronic rhinitis and bronchiectasis accounted for 93.9%, sinusitis for 90.9%, otitis media for 45.5%, hearing loss for 21.2%, and the visceral transposition for 69.7%. Out of 4 adult males, 3 were clearly recorded as infertile. Abnormal cilia morphology was found in the well-documented cased. <b>Conclusions:</b> Minigene splicing variant analysis confirmed that mutation in the intron region of the <i>DNAH5</i> gene could affect its mRNA splicing, providing evidence for the pathogenicity of the mutation site (PVS1). The <i>DNAH5</i> c.1731-18A>G mutation and c.1933C>T (p.Gln645*) compound heterozygous variations could be the genetic etiology.