Variant Synonymizer: Platform to identify mutations defined in different ways is available now!

VarSy

Over 2,000 gene–disease validation summaries are now available—no login required!

Browse Summaries

NLRP3 – Keratitis Fugax Hereditaria

Keratitis fugax hereditaria is a recurrent, autosomal dominant corneal dystrophy characterized by transient peripheral arcus-like degeneration and central stromal opacification. Until now, all reported cases were of Finnish descent and associated with exon 1 variants in NLRP3. Clinical examination with slit-lamp biomicroscopy and anterior segment optical coherence tomography in a 52-year-old non-Finnish female proband revealed peripheral arcus-like degeneration and bilateral central corneal stromal opacification (HP:0001101; HP:0010059).

Genetic testing identified a novel heterozygous NLRP3 missense variant, c.1712G>T (p.Gly571Val), confirmed de novo as it was absent in both unaffected parents (1 proband) ([PMID:37823852]). No additional affected relatives were reported. Functional studies specific to corneal pathology are lacking. Given the single case and absence of segregation data, the evidence supports a Limited association.

Key Take-home: Awareness of NLRP3 genetic heterogeneity beyond Finnish cohorts informs diagnosis of keratitis fugax hereditaria in diverse populations.

References

  • Cornea • 2024 • Keratitis Fugax Hereditaria Associated With a Novel NLRP3 Mutation in a Non-Finnish Patient PMID:37823852

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single unrelated proband with de novo missense variant and no additional segregation or functional data

Genetic Evidence

Limited

One case report; novel heterozygous missense variant c.1712G>T (p.Gly571Val) confirmed de novo ([PMID:37823852])

Functional Evidence

Limited

No functional assays reported for corneal phenotype