A new TRPV3 missense mutation in a patient with Olmsted syndrome and erythromelalgia.
OBJECTIVE
Olmsted syndrome (OS) is a rare keratinizing disorder characterized by excessive epidermal thickening of the palms and soles, with clinical and genetic heterogeneity. Approximately 50 cases have been reported, with the molecular basis described in only 9. Recently, TRPV3 (transient receptor potential vanilloid 3) mutations were identified in autosomal-dominant OS in 7 sporadic cases and 1 familial case, whereas an MBTPS2 (membrane-bound transcription factor protease, site 2) mutation was reported in X-linked recessive OS. We report a new sporadic case of severe, atypical OS and its underlying genetic basis.


METHODS
Our patient is a young girl with severe nonmutilating (palmo)plantar keratoderma without periorificial keratotic plaques associated with intense acute flares of inflammation, itching, burning pain, vasodilatation, and redness of the extremities consistent with erythromelalgia. Whole exome sequencing of patient DNA identified a novel de novo heterozygous missense mutation within TRPV3, p.Leu673Phe, predicted to be damaging.


CONCLUSIONS
This case study further implicates TRPV3 in OS pathogenesis. In addition, previous reports of OS have not described erythromelalgia as a clinical feature. Its occurrence in our patient could be a chance event, but, if associated with OS, the features of erythromelalgia may expand the phenotypic spectrum of this rare syndrome.
Institut National de la Santé et de la Recherche Médicale, U781, Paris, France2Université Paris Descartes-Sorbonne Paris Cité, Paris, France3Institut Imagine, Paris, France.
Sabine
S
Duchatelet
Université Paris Descartes-Sorbonne Paris Cité, Paris, France4Genomics Platform, Institut Imagine, Paris, France.
Solenn
S
Pruvost
Institut National de la Santé et de la Recherche Médicale, U781, Paris, France2Université Paris Descartes-Sorbonne Paris Cité, Paris, France3Institut Imagine, Paris, France.
Simon
S
de Veer
Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Sylvie
S
Fraitag
Université Paris Descartes-Sorbonne Paris Cité, Paris, France6Bioinformatics Platform, Institut Imagine, Paris, France.
Patrick
P
Nitschké
Université Paris Descartes-Sorbonne Paris Cité, Paris, France4Genomics Platform, Institut Imagine, Paris, France.
Christine
C
Bole-Feysot
Université Paris Descartes-Sorbonne Paris Cité, Paris, France3Institut Imagine, Paris, France7Department of Dermatology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France8National Reference Centre for Genodermatoses (MA.
Christine
C
Bodemer
Institut National de la Santé et de la Recherche Médicale, U781, Paris, France2Université Paris Descartes-Sorbonne Paris Cité, Paris, France3Institut Imagine, Paris, France9Department of Genetics, Necker-Enfants Malades Hospital, Assistance Publique-Hôpit.
Alain
A
Hovnanian
D000293:Adolescent; D001707:Biopsy, Needle; D018450:Disease Progression; D004916:Erythromelalgia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007645:Keratoderma, Palmoplantar / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D035583:Rare Diseases; D018570:Risk Assessment; D012720:Severity of Illness Index; D013577:Syndrome; D050916:TRPV Cation Channels / Q000235:genetics*
D050916:TRPV Cation Channels; C459445:TRPV3 protein, human