Ichthyosis, psoriasiform dermatitis, and recurrent fungal infections in patients with biallelic mutations in PERP

• Published in: Journal of the European Academy of Dermatology and Venereology Vol. 36; no. 3; pp. 472 - 479
• Main Authors: Youssefian, L., Khodavaisy, S., Khosravi‐Bachehmir, F., Park, J.S., Saeidian, A.H., Mahmoudi, H., Saffarian, Z., Naraghi, Z.S., Kamyab‐Hesari, K., Zeinali, S., Vahidnezhad, H., Uitto, J.
• Format: Journal Article
• Language: English
• Published: England 01-03-2022
• Subjects: dermatomycoses; Eczema - genetics; Genes, Tumor Suppressor; Humans; ichthyosis; Ichthyosis - genetics; Ichthyosis - pathology; Iran; Membrane Proteins - genetics; Mutation; Mycoses; Pedigree; PERP; Psoriasiform dermatitis; psoriasis; Iran; dermatomycoses; ichthyosis; PERP; psoriasis; Psoriasiform dermatitis
• DOI: 10.1111/jdv.17856
• EISSN: 1468-3083
• ISSN: 0926-9959

Background
Germline autosomal dominant and autosomal recessive mutations in PERP, encoding p53 effector related to PMP‐22 (PERP), a component of epidermal desmosomes, have been associated with a spectrum of keratodermas. Monoallelic nonsense mutations cause Olmsted syndrome with severe periorificial keratoderma and palmoplantar keratoderma (PPK). Biallelic recessive frameshift and missense mutations are associated with milder forms of the disease, including generalised erythrokeratoderma and PPK.
Objectives
To add new insights into the genotype‐phenotype correlations as a consequence of PERP mutations and to provide a comprehensive review of the literature.
Methods
Among 26 previously unresolved families within a cohort of 180 extended Iranian families with syndromic or non‐syndromic ichthyosis, two families with shared clinical features were examined by whole‐exome sequencing and genome‐wide homozygosity mapping. Mycological and dermatopathological studies were performed to further characterise their atypical phenotypic presentations.
Results
In two unrelated multiplex consanguineous families affected by ichthyosis, two novel biallelic PERP variants, NM_022121.5, c.89T > C, p.Leu30Pro and c.466G > C, p.Gly156Arg, located inside of genomic homozygosity regions of the probands were detected. Interestingly, some patients had areas of scaly psoriasiform plaques on the background of generalised ichthyosis that appeared during active cutaneous fungal infections. Mycological examinations of these lesions revealed infections caused by Candida albicans, Epidermophyton floccosum, or Trichophyton rubrum. Histopathology of the psoriasiform lesions shared some features with psoriasis, which when combined with clinical presentation, led to incorrect diagnosis of guttate psoriasis or pustular psoriasis.
Conclusions
PERP variants in ichthyosis patients can confer susceptibility to recalcitrant cutaneous fungal infections. Additionally, patients with episodic psoriasiform dermatitis in the setting of keratoderma should be considered for PERP genotyping and cutaneous fungal examinations.