| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mendeliome v1.3023 | KRT32 | Bryony Thompson Marked gene: KRT32 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3023 | KRT32 | Bryony Thompson Gene: krt32 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3023 | KRT32 | Bryony Thompson Classified gene: KRT32 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3023 | KRT32 | Bryony Thompson Gene: krt32 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3022 | KRT32 |
Bryony Thompson gene: KRT32 was added gene: KRT32 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KRT32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KRT32 were set to 40814173; 39048559 Phenotypes for gene: KRT32 were set to loose anagen syndrome MONDO:0010908; Pityriasis rubra pilaris MONDO:0100017 Review for gene: KRT32 was set to GREEN Added comment: Sufficient evidence for Pityriasis rubra pilaris association, but limited for association with loose anagen syndrome. PMID: 39048559 - Significant enrichment of KRT32 variants (p=3.06e-4) in 58 PRP cases vs 364 healthy controls (4 variants - individual 1: c.344G>A (p.Arg115Gln - 10 hets gnomAD v4.1), individual 2: c.477_478del (p.Thr160fs), individual 3: c.607C>T (p.Arg203Cys - 71 hets gnomAD v4.1), and individual 4: c.685T>C (p.Cys229Arg - 18 hets gnomAD v4.1). Validation cohort of 44 PRP cases vs 436 healthy controls identified an additional 2 variants (individual 5: c.907G>A (p.Glu303Lys - 3 hets gnomAD v4.1), individual 6: c.937A>G (p.Ile313Val - 30 hets gnomAD v4.1). A combined analysis of the KRT32 gene in both the discovery and validation cohorts revealed a significant p value of 1.73 e-6. The KRT32 expression patterns (location of protein expression) were altered in PRP cases with the KRT32 variants. In vitro analysis demonstrated that the 6 variants (all located in the IF rod domain) exhibited varying degrees of attenuation in inhibiting the NF-κB signaling pathway. A Krt32 knockout mouse model recapitulates the human PRP-like phenotype. PMID: 40814173 - a single family with loose anagen hair syndrome co-segregating (c.296C>T; p.Thr99Ile) in a large family; however, the AF in the European population is 0.3% in gnomAD v4.1 (6 homozygotes), which is higher than expected for a dominant condition. In vitro functional assay showing the variant alters interaction with KRT82, however, only WT & the variant were assessed (no positive control). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||