A novel mutation in TRPV3 gene causes atypical familial Olmsted syndrome

Abstract

Olmsted syndrome (OS) is a rare keratinization disorder, typically characterized by two primary diagnostic hallmarks—mutilating palmoplanter and periorificial keratoderma. However, there’s a growing body of literature reporting on the phenotypic diversity of OS, including the absence of aforementioned hallmarks and the presence of some unusual clinical features. Here we presented an atypical familial case of OS that could be confused with Huriez syndrome due to the presence of a scleodactyly-like appearance and tapered fingers in the proband. We ruled out this possibility and made a definitive diagnosis of OS based on clinical features and a genetic assay. Recently, mutations in TRPV3 associated with autosomal dominant or recessive OS continued to be reported, thus conducing to clarifying the underlying relationship between the genotype and phenotype of OS. So we further explored the genotype-phenotype correlation by integrating functionl assays with in silico predictions. Our research not only redefined the phenotypic spectrum of OS, but also provided concrete molecular insights into how mutations in a single gene can lead to significant differences in the severity of this rare disease.

Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features

“…Extracutaneous manifestations, such as growth delay, hearing loss for high tones, abnormal dentition, bone deformities, high IgE levels, chronic eosinophilia, elevated follicular T cells in peripheral blood, have been reported in a few patients . In the last few years, 8 families with less severe phenotype have been described, presenting focal PPK and autosomal dominant TRPV3 mutations . All these cases are considered as ‘atypical Olmsted syndrome forms’ for the focal, friction‐related, aspect of PPK, absence or transient presence of periorificial hyperkeratosis, absence or only mild hair and nail abnormalities, usually no pseudoainhum or autoamputations.…”

“…119 In the last few years, 8 families with less severe phenotype have been described, presenting focal PPK and autosomal dominant TRPV3 mutations. [121][122][123] All these cases are considered as 'atypical Olmsted syndrome forms' for the focal, friction-related, aspect of PPK, absence or transient presence of periorificial hyperkeratosis, absence or only mild hair and nail abnormalities, usually no pseudoainhum or autoamputations. Ni et al 123 also described the sclerodactyly-like appearance and the cone shape of fingers, a feature reminiscent of Huriez syndrome.…”

“…[121][122][123] All these cases are considered as 'atypical Olmsted syndrome forms' for the focal, friction-related, aspect of PPK, absence or transient presence of periorificial hyperkeratosis, absence or only mild hair and nail abnormalities, usually no pseudoainhum or autoamputations. Ni et al 123 also described the sclerodactyly-like appearance and the cone shape of fingers, a feature reminiscent of Huriez syndrome. A X-linked recessive mutation in MBTPS2 (Table S1), encoding the membrane-bound transcription factor protease site 2, 124 has been recently identified in an Iranian family suffering from Olmsted syndrome, 125 originally described by Yaghoobi et al 126 ( Table 9).…”

Identification of a heterozygous p.Gly568Val missense mutation in the TRPV3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV3

“…To the best of our knowledge, this is the first report of a Japanese patient with OS who was shown to harbor a missense mutation in the TRPV3 gene. Our published work search showed that 19 cases of OS patients with a genetic mutation in the TRPV3 gene have been reported to date . The symptoms of OS are variable, even among patients with the same TRPV3 mutation, suggesting the involvement of environmental factors and/or modified genes.…”

“…Our published work search showed that 19 cases of OS patients with a genetic mutation in the TRPV3 gene have been reported to date. 6,14 The symptoms of OS are variable, even among patients with the same TRPV3 mutation, suggesting the involvement of environmental factors and/or modified genes. Indeed, a Brazilian patient with the same mutation in TRPV3, p.Gly568Val, was reported to have focal and mild/moderate palmoplantar keratodermas, 6 whereas our patient had diffuse and severe ones.…”