DNAH8 – Primary Ciliary Dyskinesia

The axonemal heavy chain gene DNAH8 has been investigated as a candidate for autosomal recessive primary ciliary dyskinesia (primary ciliary dyskinesia). To date, no biallelic pathogenic variants in DNAH8 have been reported in confirmed PCD cases, and one patient with a DNAH8/HYDIN variant demonstrated normal respiratory ciliary ultrastructure by TEM (PMID:37998386). No segregation of DNAH8 variants with PCD phenotypes has been observed, and no affected relatives have been described.

Functional localization studies show that DNAH8 colocalizes with α-tubulin along sperm axonemes but is absent from respiratory cilia, providing a mechanistic basis for its lack of involvement in chronic respiratory tract disease (PMID:31178125). These data conflict with a role for DNAH8 in PCD, as outer dynein arm composition differs between sperm and motile cilia. Overall, the evidence argues against pathogenic involvement of DNAH8 in PCD, and routine diagnostic screening for DNAH8 variants in PCD is not supported.

References

• American journal of human genetics • 2019 • Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Outer Dynein Arm Heavy Chain, Cause Isolated Male Infertility Due to Asthenozoospermia. PMID:31178125
• Cells • 2023 • Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype. PMID:37998386

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