Ichthyosis and erythrokeratoderma
Gene: TRPV3After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Green.Created: 31 Jan 2023, 2:33 p.m. | Last Modified: 31 Jan 2023, 2:33 p.m.
Panel Version: 2.12
Added Q2_21_expert_review tag as this is a proposed demotion.Created: 12 Oct 2022, 2:45 p.m. | Last Modified: 12 Oct 2022, 2:45 p.m.
Panel Version: 1.73
TRPV3 not appropriate phenotype for panel, on panel due to panel construction for GMSCreated: 26 May 2021, 5:08 p.m. | Last Modified: 26 May 2021, 5:08 p.m.
Panel Version: 1.60
Comment on phenotypes: Previous phenotypes:
Palmoplantar Keratoderma, Mutilating, with Periorificial Keratotic Plaques;?Palmoplantar keratoderma, nonepidermolytic, focal 2, 616400;Olmsted syndrome, 614594Created: 23 Mar 2021, 3:54 p.m. | Last Modified: 23 Mar 2021, 3:54 p.m.
Panel Version: 1.58
This gene is better suited to the palmoplantar keratoderma panel as this is the key feature of Olmstead syndrome. Cannot find association with ichthyosis/erythrokeratoderma.Created: 12 Aug 2020, 8:04 a.m. | Last Modified: 12 Aug 2020, 8:04 a.m.
Panel Version: 1.3
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Olmsted syndrome, MIM# 614594
Comment when marking as ready: Sufficient cases to support causation. Mode of inheritance supported by OMIM and G2P.Created: 13 Mar 2017, 10:16 a.m.
Comment on list classification: Updated rating from Amber to Green: 1 Green expert review plus at least 3 unrelated cases (from China and India) supporting causation for Olmsted Syndrome (which presents with PPK) from OMIM and additional literature. Plus one family reported for Palmoplantar keratoderma, nonepidermolytic, focal 2 (MIM:616400).Created: 13 Mar 2017, 10:16 a.m.
>3 TRPV3 variants listed in OMIM for Olmsted syndrome (OMIM:614594; also known as mutilating palmoplantar keratoderma with periorificial keratotic plaques). This includes 6 Chinese patients with OMIM:614594 identified by Lin et al., 2012 (PMID: 22405088), and a girl of unspecified ethnicity (PMID:24452206, Duchatelet et al., 2014). It's not specified whether the Chinese patients in Lin et al, are related or not.Created: 13 Mar 2017, 9:36 a.m.
TRPV3 is a PROBABLE DD gene for Olmsted syndrome (OMIM:614594).Created: 13 Mar 2017, 9:16 a.m.
PMID:25989441 (Agarwala, 2016) present a 28 year old Indian male with Olmsted syndrome and thickening of palmar and plantar skin (diffuse PPK). They detected four heterozygous variants in TRPV3. Only one of these was unique to the affected proband: c.1246Ins6 (a 6 nucleotide insertion) appears to be a de novo change that is only expressed in the proband's DNA. Other heterozygous changes are present in the unaffected parents and sister.Created: 10 Jan 2017, 3:05 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM (for both OMIM:614594 and OMIM:616400) and G2P (for Olmsted syndrome, OMIM:614594).Created: 9 Jan 2017, 9:55 a.m.
1 TRPV3 variant listed in OMIM for 'Palmoplantar keratoderma, nonepidermolytic, focal 2 (OMIM:616400)' for 1 family (also a Chinese family- a father and son with focal palmoplantar keratoderma). The mutation (a T-G transversion resulting in a Q580P substitution) occurred de novo in the father; it was not detected in the unaffected paternal grandparents, an unaffected paternal uncle, or an unaffected sister. Transfection studies suggest that Q580P is a gain-of-function change.Created: 9 Jan 2017, 9:52 a.m.
Comment on mode of pathogenicity: The T-G transversion (rs786205869) resulting in a Q580P substitution in a Chinese father and son (PMID:25285920, He et al., 2015) is a gain-of-function change.Created: 9 Jan 2017, 9:52 a.m.
Tag Q2_21_rating was removed from gene: TRPV3. Tag Q2_21_expert_review was removed from gene: TRPV3.
Tag Q2_21_expert_review tag was added to gene: TRPV3.
Tag Q2_21_NHS_review was removed from gene: TRPV3.
Tag Q2_21_rating tag was added to gene: TRPV3. Tag Q2_21_NHS_review tag was added to gene: TRPV3.
Phenotypes for gene: TRPV3 were changed from Palmoplantar Keratoderma, Mutilating, with Periorificial Keratotic Plaques; ?Palmoplantar keratoderma, nonepidermolytic, focal 2, 616400; Olmsted syndrome, 614594 to ?Palmoplantar keratoderma, nonepidermolytic, focal 2, OMIM:616400; Olmsted syndrome, OMIM:614594
gene: TRPV3 was added gene: TRPV3 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: TRPV3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPV3 were set to 25285920 Phenotypes for gene: TRPV3 were set to Palmoplantar Keratoderma, Mutilating, with Periorificial Keratotic Plaques; ?Palmoplantar keratoderma, nonepidermolytic, focal 2, 616400; Olmsted syndrome, 614594 Mode of pathogenicity for gene: TRPV3 was set to Other - please provide details in the comments