Ectodermal dysplasia
Gene: KRT83Comment on list classification: KRT81 is associated with two relevant phenotypes in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification for monilethrix. Monoallelic variant have been linked to monilethrix in two families (PMID: 15744029; 25557232) while biallelic variants were found in one family with EKVP5 (PMID: 27965375).
Overall no additional evidence has been published since the last review and therefore going to maintain the amber rating for now, but adding a 'watchlist' tag to monitor for additional evidence that may lead to future upgrade to green.
Other keratin genes, like KRT81 and KRT86 have been added as amber with the recommendation of being made green at the next review.Created: 6 Nov 2023, 2:45 p.m. | Last Modified: 6 Nov 2023, 2:45 p.m.
Panel Version: 3.22
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, 11:05 a.m. | Last Modified: 18 Sep 2023, 11:05 a.m.
Panel Version: 3.8
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Monilethrix
Publications
KRT83 is in OMIM with relevant phenotype of Monilethrix, KRT83 is part of a family of genes with KRT86 and KRT81 with this phenotype. Less than three individuals identified in KRT83 with phenotype of Monilethrix.
In OMIM in a monoallelic form KRT83 variant has been reported in one Pakistani kindred, associated with Erythrokeratodermia variabilis et progressiva, all family members had normal hair, teeth, and sweating therefore different phenotype.
As neither phenotype has more than three variants identified KRT83 will be classified as Amber.Created: 3 Dec 2019, 12:40 p.m. | Last Modified: 3 Dec 2019, 12:43 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:KRT83; 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
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Monilethrix, 158000; Erythrokeratodermia variabilis et progressiva, 617756
Tag watchlist tag was added to gene: KRT83.
Gene: krt83 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: KRT83 were changed from to Monilethrix, OMIM:158000
Publications for gene: KRT83 were set to
Mode of inheritance for gene: KRT83 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
gene: KRT83 was added gene: KRT83 was added to Ectodermal dysplasia. Sources: Expert Review Amber Mode of inheritance for gene: KRT83 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown