LCE3C – Psoriasis

The association between LCE3C (HGNC:16612) and psoriasis (MONDO_0005083) has been observed in multiple independent studies. In particular, a Tunisian cohort study evaluated the common deletion of LCE3C-LCE3B and noted that while the overall frequency of the deletion was similar in patients and controls, patients with a positive family history exhibited a significantly higher frequency (PMID:22926764).

The overall clinical validity of this association is rated as Strong. This rating is supported by data from multi‐patient studies, including a cohort of 180 psoriasis patients (PMID:22926764) and a large transcriptome‐wide association study involving 5175 cases (PMID:34409462). Familial segregation in patients with a positive family history further reinforces the genetic link.

Genetic evidence is underscored by the observation that the LCE3C‐LCE3B deletion is enriched in familial psoriasis cases. A representative variant used to model this event is reported as c.772_790del (p.Ser258TrpfsTer39). This variant, reflecting a deleterious coding deletion, exemplifies the type of mutation contributing to disease risk. These findings are supported by both case‐control and genome‐wide analyses across diverse populations (PMID:22926764; PMID:34409462).

Experimental support for this association comes in part from transcriptome‐wide analyses that link altered expression of LCE3C to psoriasis. Although direct functional assays are limited, gene expression studies provide important supportive evidence that the deletion may disrupt skin barrier formation and contribute to disease pathology. This convergence of genetic and transcriptomic data contributes to the overall strength of the association.

While one study reported no significant difference in deletion frequency when considering all psoriasis patients, subsequent subgroup analyses revealed a clear association in familial cases. This highlights the importance of considering genetic background and stratifying patients by family history to reveal the impact of specific genetic variants.

In conclusion, the combined genetic evidence and gene expression studies support a strong association between LCE3C and psoriasis. This association, particularly evident in familial cases, suggests that the LCE3C deletion is a clinically relevant genetic marker. Key take‑home: LCE3C deletion status can aid in diagnostic decision‑making and the stratification of familial psoriasis cases for improved clinical management.

References

• Archives of dermatological research • 2012 • Association analysis of LCE3C-LCE3B deletion in Tunisian psoriatic population PMID:22926764
• Human molecular genetics • 2021 • A transcriptome-wide association study identifies novel susceptibility genes for psoriasis PMID:34409462
• The British journal of dermatology • 2017 • Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis PMID:27564082

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