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Ectodermal dysplasia v3.22 KRT83 Arina Puzriakova Added comment: Comment 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.
Ectodermal dysplasia v3.20 KRT81 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: KRT81.
Tag Q4_23_NHS_review tag was added to gene: KRT81.
Ectodermal dysplasia v3.20 KRT81 Arina Puzriakova Publications for gene: KRT81 were set to
Ectodermal dysplasia v3.19 KRT81 Arina Puzriakova Classified gene: KRT81 as Amber List (moderate evidence)
Ectodermal dysplasia v3.19 KRT81 Arina Puzriakova Added comment: 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.
Ectodermal dysplasia v3.19 KRT81 Arina Puzriakova Gene: krt81 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v3.15 KRT81 Arina Puzriakova Phenotypes for gene: KRT81 were changed from to Monilethrix, OMIM:158000
Ectodermal dysplasia v3.8 KRT81 Ronnie Wright reviewed gene: KRT81: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 9665406, 9402962; Phenotypes: Monilethrix; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal dysplasia v3.8 KRT86 Ronnie Wright gene: KRT86 was added
gene: KRT86 was added to Ectodermal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: KRT86 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT86 were set to PMID: 10469314; 10594761; 10504448; 12653715
Phenotypes for gene: KRT86 were set to Monilethrix
Penetrance for gene: KRT86 were set to Incomplete
Review for gene: KRT86 was set to GREEN
Added comment: 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 few publications for KRT81 and KRT83 but I think there are sufficient for KRT86 and for all 3 genes 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/).
Sources: NHS GMS
Ectodermal dysplasia v0.34 KRT83 Catherine Snow changed review comment from: KRT81 is in OMIM with relevant phenotype of Monilethrix, KRT81 is part of a family of genes with KRT86 and KRT83 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.; to: 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.
Ectodermal dysplasia v0.34 KRT83 Catherine Snow edited their review of gene: KRT83: Added comment: KRT81 is in OMIM with relevant phenotype of Monilethrix, KRT81 is part of a family of genes with KRT86 and KRT83 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.; Changed phenotypes: Monilethrix, 158000, Erythrokeratodermia variabilis et progressiva, 617756; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ectodermal dysplasia v0.34 KRT81 Catherine Snow changed review comment from: 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. KRT81 currently classified as Amber as less than 3 unrelated individuals identified.; to: 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.
Ectodermal dysplasia v0.33 KRT81 Catherine Snow edited their review of gene: KRT81: Added comment: 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. KRT81 currently classified as Amber as less than 3 unrelated individuals identified.; Changed publications: 9402962, 9665406; Changed phenotypes: Monilethrix
Ectodermal dysplasia v0.21 KRT81 Catherine Snow reviewed gene: KRT81: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ectodermal dysplasia v0.15 KRT81 Catherine Snow gene: KRT81 was added
gene: KRT81 was added to Ectodermal dysplasia. Sources: Expert Review Amber
Mode of inheritance for gene: KRT81 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown