PCP2 – Relapsing Polychondritis

A family‐based whole‑exome sequencing study has identified PCP2 (HGNC:30209) as a candidate gene in relapsing polychondritis (MONDO:0019125). In a Chinese family, a 32‑year‑old affected proband and her affected mother were evaluated, and among nine single nucleotide polymorphism variants identified, a variant in PCP2 (rs144974437) was noted as a potential contributor to disease predisposition (PMID:32107856). Although the reported variant for PCP2 is derived from a larger multigene panel, the limited segregation data—in which only one additional affected relative was documented—restricts the robustness of the genetic association. The inheritance pattern in this family appears to be autosomal dominant, given the vertical transmission from mother to daughter. The case‐report and multi‑patient study provide only modest genetic evidence with respect to the number of unrelated probands and the extent of segregation.

No direct functional assays were performed to assess the pathogenic consequences of the PCP2 variant in the context of cartilage homeostasis or immune regulation in relapsing polychondritis. Consequently, the functional evidence remains limited, and the mechanistic role of PCP2 in disease pathology is yet to be elucidated. Integration of the genetic findings with the absence of direct in vitro or in vivo functional data underscores a tentative link that requires further research. Overall, the available data support a limited association between PCP2 and relapsing polychondritis, emphasizing the need for independent replication and additional functional validation. Key take‑home: While preliminary genetic evidence implicates PCP2 in relapsing polychondritis, its clinical utility awaits more robust corroborative data.

References

• International journal of rheumatic diseases • 2020 • Genetic basis of relapsing polychondritis revealed by family‑based whole‑exome sequencing PMID:32107856

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