We have previously shown that gain-of-function variations in transient receptor potential vanilloid-3 (TRPV3) underlay Olmsted syndrome, a rare hyperkeratotic skin channelopathy. In this study, we attempt to establish a genotype‒phenotype correlation in Olmsted syndrome, which has been unclear owing to the rarity and heterogeneity of the condition. We identified five previously unreported TRPV3 variations (R416Q, R416W, L655P, W692S, and L694P) and three recurrent variations (G568D, G568V, and L673F) in nine unrelated patients. Seven variants were expressed in human embryonic kidney 293 cells, and channel behavior was characterized electrophysiologically, with results compared with the clinical severity. These variant TRPV3 channels, in either homomeric or heteromeric form, exhibited differentially elevated basal open probability, increased voltage sensitivity, and cytotoxicity. Functional changes were particularly pronounced in variants corresponding to severer Olmsted syndrome (e.g., L673F and W692S) but not in mild Olmsted syndrome variants (e.g., R416Q). Interestingly, the extent of functional rescue by wild-type TRPV3 in vitro was also consistent with the clinical severity of the variants. These findings, in combination with all reported cases, indicate a preliminary genotype‒phenotype correlation, that is, variations in the S4‒S5 linker and transient receptor potential domain of TRPV3 significantly enhance channel function, causing severe phenotype, whereas other variations appear to exert milder effects on channel function and disease phenotype.
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http://dx.doi.org/10.1016/j.jid.2020.06.035 | DOI Listing |
J Rheumatol
January 2025
Floranne C. Ernste MD, Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
Objective: Population-based epidemiology studies about antisynthetase syndrome (ASSD) are lacking. Our aims were to determine the incidence and prevalence of ASSD and assess malignancy risk among patients following ASSD diagnosis.
Methods: A retrospective, population-based cohort of adults with incident ASSD residing in Olmsted County, Minnesota, in 1998-2019 was assembled.
Front Genet
December 2024
Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, China.
Olmsted syndrome is characterized by symmetrically distributed, destructive, inflammatory palmoplantar keratoderma with periorificial keratotic plaques, most commonly due to gain-of-function mutations in the transient receptor potential vanilloid 3 (TRPV3) gene, which involves multiple pathological functions of the skin, such as hyperkeratosis, dermatitis, hair loss, itching, and pain. Recent studies suggest that mutations of located in different structural domains lead to cases of varying severity, suggesting a potential genotype-phenotype correlation resulting from TRPV3 gene mutations. This paper reviews the genetics and pathogenesis of Olmsted syndrome, as well as the potential management and treatment.
View Article and Find Full Text PDFJ Dermatol Sci
December 2024
Genetic Skin Disease Center, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. Electronic address:
Diabetes Obes Metab
February 2025
Department of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota, USA.
Aims: Define the relationship between N-terminal atrial natriuretic peptide (NT-ANP) levels and incident metabolic syndrome and type 2 diabetes mellitus ('metabolic disease') in healthy adults and develop a risk prediction score.
Materials And Methods: Retrospective cohort study of Olmsted County Heart Function Study participants, a random sampling of county residents aged 45 years and older (n = 2042). Clinical data were collected during enrolment between 1997 and 2000 and upon follow-up 4 years later.
J Dermatol Sci
December 2024
Genetic Skin Disease Center, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. Electronic address:
Background: Olmsted syndrome (OS) is a rare genodermatosis predominantly inherited in an autosomal dominant manner, typically arising from gain-of-function (GOF) variants in the transient receptor potential channel vanilloid 3 (TRPV3) gene.
Objective: This study aims to investigate potential mechanisms underlying OS in two cases presenting with an autosomal recessive inheritance pattern.
Methods: Next-generation sequencing panel was employed to identify TRPV3 variants.
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