KRT1 – Ichthyosis Hystrix of Curth-Macklin

A single unrelated individual with autosomal dominant ichthyosis hystrix of Curth-Macklin was reported to carry a novel heterozygous frameshift mutation in KRT1, c.1596_1597insAT (p.Gly533MetfsTer82), resulting in replacement of the glycine-serine–rich tail with an alanine-rich sequence and a mild phenotype of localized ichthyosis and progressive palmoplantar hyperkeratosis without blistering (PMID:32049370). No familial segregation or functional assays beyond predicted protein alteration have been described.

Given only one proband and absence of segregation or experimental confirmation, the clinical validity is Limited. Genetic evidence is Limited based on one AD case with a truncating tail‐domain variant. Functional evidence remains Limited—pathogenicity is inferred from predicted disruption of the V2 tail but lacks in vitro or in vivo validation.

Key Take-home: KRT1 c.1596_1597insAT (p.Gly533MetfsTer82) identifies KRT1 as a causative gene for Curth-Macklin ichthyosis but requires additional familial and functional studies to solidify clinical utility.

References

• Clinical and experimental dermatology • 2020 • A novel frameshift truncation mutation in the V2 tail domain of KRT1 causes mild ichthyosis hystrix of Curth-Macklin. PMID:32049370

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