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The patients in this manuscript have given written informed consent to publication of their case details. Although these syndromes are very rare, Netherton syndrome, Sjögren-Larsson syndrome, Conradi-Hünermann-Happle syndrome, among others, have been described as representative ones.10 We present the first known case of PSD with splice mutation in the CDSN gene. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Summary: Background: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype–phenotype correlation in some populations. Objectives: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype–phenotype correlation. Methods: Deep phenotyping was undertaken by history‐taking and clinical examination. DNA was screened for mutations using a next‐generation sequencing ichthyosis gene panel and Sanger sequencing. Results: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self‐improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. Conclusions: These data refine genotype–phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose.Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1.Some phenotypic features may associate with certain gene mutations, but paradigms for genotype–phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%).New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision.In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown. Linked Editorial:Steele and O'Toole. Br J Dermatol 2020; 182:521–522. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Recessive dystrophic epidermolysis bullosa (RDEB; OMIM #226600) is one of the most devastating subtypes of epidermolysis bullosa, a group of skin and mucous membrane blistering disorders often associated with extracutaneous manifestations. RDEB is caused by mutations in COL7A1, the gene encoding type VII collagen (C7), and to date over 700 different mutations in the 8835 nucleotides constituting the open reading frame or adjacent exon–intron boundaries of COL7A1 have been described. We used targeted next‐generation sequencing to identify seven previously unreported mutations in a cohort of 17 Mexican patients who were diagnosed with RDEB based on clinical presentation and immunoepitope mapping. Our study expands the spectrum of mutations identified in this cohort, including those suitable for emerging therapies reliant on precise genotyping. [ABSTRACT FROM AUTHOR]

Summary: Pachyonychia congenita (PC) is a rare autosomal dominant disorder characterized by nail dystrophy and palmoplantar keratoderma with severe plantar pain affecting quality of life. There is no effective treatment. Heterozygous mutations in the keratin genes KRT6A, KRT6B, KRT6C, KRT16 and KRT17 have been reported as a cause of PC. Herein we present a female patient with an amino acid substitution mutation in KRT6A (c.1381G>A, p.Glu461Lys in exon 7) and classic features of PC associated with oral leucokeratosis and follicular hyperkeratosis. We also demonstrate successful treatment of the patient with rosuvastatin. A 3.6‐mm reduction in plantar callosity thickness was demonstrated by sonography. Our patient also experienced significant pain relief that allowed her to increase physical activity (Children's Dermatology Life Quality Index score dropped nine points following treatment). Collectively, these improvements suggest that rosuvastatin may offer a promising treatment for PC. What's already known about this topic? Pachyonychia congenita (PC) is an autosomal dominant disease characterized by nail dystrophy and painful plantar keratoderma.Keratolytics, emollients, retinoids and steroids have been used for treatment but with limited benefits. What does this study add? A patient with PC who had a KRT6A mutation was treated with rosuvastatin with significant improvement in plantar hyperkeratosis and pain.Statins could be a promising treatment for PC with long‐term safety, but further studies are needed. Linked Comment: Theocharopoulos and O'Toole. Br J Dermatol 2019; 181:446–447. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study on the congenital mosaic tissue overgrowth related to the PIK3CA gene mutation.

The article offers information on recessive dystrophic epidermolysis bullosa (RDEB)which is an autosomal recessive disorder characterized by skin fragility, It ststes that RDEB lead to trauma-induced blisters and heal with scarring and fibrosis. It states that patients can have nail dystrophy, pseudosyndactyly and anaemia due to oesophageal strictures.

The article presents a case study of three patients having mutations in ichthyosis-related genes involved in lipid metabolism who presented with erythrokeratoderma. In one of the patients, same mutation in PNPLA1 was found in an additional family in the cohort with two siblings suffering from mild ichthyosis.

Infantile systemic hyalinosis ( ISH) is an extremely rare genodermatosis, characterized by thickened skin, joint contractures and subcutaneous nodules. ISH is caused by mutations in the CMG2 gene, which encodes a protein of unknown function. In this report, we describe a patient with ISH, who was a twin born to a consanguineous Iranian couple, and who demonstrated unusual skin findings in addition to the characteristic features of ISH. Mutation analysis disclosed a homozygous deletion mutation, c.1074delT in CMG2, resulting in a frameshift and premature termination codon 50 amino acids downstream of the deletion. This information adds to the recurring nature of this mutation in ISH, with implications for genetic counselling in extended families with a history of this disease. [ABSTRACT FROM AUTHOR]

Linked Article:Goldberg et al. Br J Dermatol 2020; 182:708–713. [ABSTRACT FROM AUTHOR]

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Summary: Ichthyosis is a disorder in which the skin is very thick and scaly. It is usually caused by a genetic mistake (mutation). "Autosomal recessive" ichthyosis occurs when parents who are healthy carriers both pass on a mutant gene to their child, so the child inherits a double dose of the mutation and cannot make normal skin. Scientists have already discovered mutations in 13 genes that cause ichthyosis. This study looks at whether the type of mutation (genotype) tells us anything about the type of ichthyosis (phenotype). The doctors examined 146 ichthyosis patients, average age 17 years, from 124 families, recruited from 13 English hospitals. They extracted DNA from blood or saliva. They found mutations in 83% of patients; the other 17% presumably have mutations not detectable by current techniques or in different genes. There were mutations in 10 different ichthyosis genes, mostly a gene called TGM1. To some extent different genotypes corresponded to different phenotypes. TGM1 ichthyosis usually has large, brown scales while ALOX12B mutations cause fine white scaling. ABCA12 mutations cause more severe ichthyosis, including the very serious harlequin type with distorted fingers; by contrast patients with milder ichthyosis usually had TGM1 or ALOX12B mutations. Nearly half of the babies with ALOX12B mutations were born with the top of their ear folded over. Some TGM1 patients had abnormally red skin while others with exactly the same mutation did not. In conclusion, this large study provides a lot of new information about ichthyosis, but genotype only partly predicts phenotype. This is a summary of the study: Genotype–phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis Linked Article: Simpson et al. Br J Dermatol 2020; 182:729–737 [ABSTRACT FROM AUTHOR]