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DNAJB13 – Primary Ciliary Dyskinesia

The DNAJB13 gene is associated with Primary Ciliary Dyskinesia (PCD) in an autosomal-recessive manner. Two unrelated probands presenting with recurrent respiratory-tract infections and male infertility were found to harbor homozygous biallelic variants: a missense change, c.833T>G (p.Met278Arg), and a canonical splice-site mutation, c.68+1G>C, each segregating with PCD characterized by central complex defects (PMID:27486783). Functional assays demonstrated that the p.Met278Arg substitution induces protein instability, proteasomal degradation, and absence of endogenous DNAJB13 in patient cilia and sperm, consistent with a loss-of-function mechanism (PMID:27486783).

This body of evidence supports a Limited level of clinical validity, based on two case-level observations with confirmed biallelic variants and strong concordant functional data. Additional reports and larger cohorts are needed to elevate the association. Key Take-home: Biallelic DNAJB13 variants can underlie PCD, informing molecular diagnosis and genetic counseling.

References

  • American journal of human genetics • 2016 • Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause Primary Ciliary Dyskinesia and Male Infertility. PMID:27486783

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Two unrelated probands with homozygous DNAJB13 variants and consistent PCD phenotypes, supported by functional studies

Genetic Evidence

Limited

Case-level data: 2 probands with biallelic variants (one missense, one splice)

Functional Evidence

Moderate

In vitro assays show p.Met278Arg induces protein instability, loss in cilia and sperm, consistent with loss-of-function