Ectodermal dysplasia

Gene: KRT81

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 6 Dec 2024, 12:48 p.m. | Last Modified: 6 Dec 2024, 12:48 p.m.

Panel Version: 3.35

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Comment on list classification: KRT81 is associated with a relevant phenotype in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification. Monoallelic variant have been linked to monilethrix. In addition to the two families previously discussed (PMID: 9665406; 9402962), there are an additional three unrelated cases reported in the literature (PMID: 10504448; 14714571; 25557232), particularly for recurrent variants at p.Glu413. KRT81 variants have been found in unaffected family members, suggesting reduced penetrance.
Overall there are sufficient cases to support an association with monilethrix, and therefore this gene can be promoted to Green at the next GMS panel update.

Created: 6 Nov 2023, 2:32 p.m. | Last Modified: 6 Nov 2023, 2:32 p.m.

Panel Version: 3.19

I don't know

We've had clinician enquiries in North West GLH about Keratin Genes associated with Monilethrix (see also KRT81 and KRT83) not being present in Ectodermal dysplasia panel. It may be worth reviewing the evidence for all 3 of these genes. There are fewer publications for KRT81 and KRT83 than KRT86 but the reported variants seem to be consistent with pathogenic enriched regions in Keratin genes (see PER viewer for whole Keratin gene family https://per.broadinstitute.org/)

Created: 18 Sep 2023, 11:08 a.m. | Last Modified: 18 Sep 2023, 11:08 a.m.

Panel Version: 3.8

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Monilethrix

Publications

• PMID: 9665406
• 9402962

I don't know

KRT81 is in OMIM with relevant phenotype of Monilethrix. Two publications detailing two separate families, which reported that penetrance is variable and one family member had the variant but no reported symptoms, therefore classifying KRT81 as Amber.

Created: 3 Dec 2019, 11:20 a.m. | Last Modified: 3 Dec 2019, 12:19 p.m.

Panel Version: 0.34

This gene was part of a gene list collated by John McGrath, KCL and Veronica Kinsler, UCL, 17.Jun.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted:KRT81; Suggested initial gene rating: Green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.

Created: 9 Sep 2019, 3:38 p.m. | Last Modified: 9 Sep 2019, 3:38 p.m.

Panel Version: 0.21

Phenotypes
Monilethrix

Publications

• 9402962
• 9665406