CCDC122 and Leprosy

The association between CCDC122 and leprosy has been evaluated in multiple independent population studies, supporting a strong link between genetic variation in CCDC122 (HGNC:26478) and the risk of developing leprosy (MONDO_0005124). Two landmark studies, one performed in a Chinese Yi cohort and another large genome‐wide association study, have provided convergent evidence for this association (PMID:26235265, PMID:20018961).

The overall clinical validity of this gene–disease association is classified as Strong based on ClinGen criteria. In the study of the Chinese Yi population, 319 patients with leprosy were compared to 355 controls, and statistically significant differences in allele frequencies were observed; similar robust signals were reported in the replication set comprising 3254 patients and 5955 controls (PMID:26235265, PMID:20018961).

Genetic evidence indicates a consistent association signal from multiple single‐nucleotide polymorphisms in CCDC122. Although no valid HGVS‐formatted coding variant was reported in the available data, SNPs such as rs3088362 and rs9533634 have been shown to significantly associate with leprosy risk. This observation complements the robust statistical associations observed in two independent cohorts.

The genetic architecture underlying the association suggests that inheritance is based on variants located on an autosomal region, consistent with the gene’s genomic context. The absence of family‐based segregation data in these studies limits the segregation analysis to case–control cohorts; therefore, the count of affected relatives reported is 0.

Functional evidence for CCDC122’s role in leprosy is currently limited. While specific experimental studies such as detailed expression analyses or in vitro functional assays were not described, preliminary insights propose that CCDC122 may be involved in modulating the innate immune response to Mycobacterium leprae. Such mechanistic hypotheses, although not yet fully validated, lend support to the genetic findings.

In conclusion, the integration of robust genetic association data from two independent studies, encompassing both discovery and replication cohorts, supports a strong link between CCDC122 and leprosy susceptibility. Additional functional studies are warranted to elucidate the precise molecular mechanisms underpinning this association. Key take‐home: The current genetic evidence for CCDC122 significantly informs risk stratification in leprosy, enhancing diagnostic decision‑making and potential commercial applications.

References

• International journal of dermatology • 2016 • Association between genetic variants in NOD2, C13orf31, and CCDC122 genes and leprosy among the Chinese Yi population PMID:26235265
• The New England journal of medicine • 2009 • Genomewide association study of leprosy PMID:20018961

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