NME8 – Primary Ciliary Dyskinesia

NME8 encodes a thioredoxin-nucleoside diphosphate kinase (TXNDC3) essential for axonemal integrity. In a single autosomal recessive PCD family, 1 proband exhibited compound transallelic defects—c.271-27C>T and c.1277T>A (p.Leu426Ter)—segregating with disease ([PMID:17360648]). No additional affected relatives were described. Targeted sequencing of NME8 in 7 Kartagener syndrome probands ([PMID:18270537]) and broader PCD cohorts ([PMID:19410201]) identified no pathogenic variants, indicating lack of replication.

Functional assays in patient cells demonstrated an intronic SNP–induced shift in TXNDC3 splice isoform ratio with reduced TXNDC3d7 expression and loss of microtubule binding, consistent with a loss-of-function mechanism ([PMID:17360648]). No recurrent or founder alleles have been reported, and variant prevalence remains undefined. Although experimental data are concordant, evidence is limited to a single family without replication, yielding a Limited clinical validity.

Key take-home: Screening for NME8 splice-modulating and truncating variants may aid diagnosis in rare PCD cases, but further familial and population studies are required.

References

• Proceedings of the National Academy of Sciences of the United States of America • 2007 • A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia. PMID:17360648
• European Journal of Human Genetics • 2008 • Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q. PMID:18270537
• Paediatric Respiratory Reviews • 2009 • Ciliary defects and genetics of primary ciliary dyskinesia. PMID:19410201

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