Submission Details

Primary Ciliary Dyskinesia (PCD) is a genetically heterogeneous disease caused by structural and motility defects of cilia in the airway cells (Whitfield et al., 2019). Ciliary defects are the consequence of mutations in one of many genes, such as damong which Dynein heavy chains genes. DNAH8 is one of the axonemal outer dynein arm heavy chains (DHC) (Whitfield et al., 2019). Only one PCD patient with a homozygous nonsense mutation in DNAH8 was reported in the literature (Watson et al., 2014, PMID: 24307375). The clinical features, age, gender/sex and fertility status of the patient were not detailed. Therefore, the score of this genetic evidence was downgraded to zero. Moreover, many pieces of evidence (Western blot, Immunostaining, RT-PCR) prove that DNAH8 is expressed in sperm flagella but not in the lungs or the Fallopian tubes (Whitfield et al., 2019, PMID:31178125 and Uhlen et al., 2015, PMID: 25613900). The same expression profile is observed in mice, where the mice orthologue of DNAH8 (DNAHC8) is expressed in testis but not in the lungs (Yang et al., 2020, PMID: 32681648). In summary, the evidence supporting the relationship between DNAH8 and autosomal recessive Primary Ciliary Dyskinesia has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role DNAH8 plays in this disease. This classification was approved by the ClinGen Motile Ciliopathy GCEP on June 23, 2022 (SOP Version 8).