Recessive epidermolytic ichthyosis results from loss of keratin 10 expression, regardless of the mutation location

Vodo, Dan; Sarig, Ofer; Peled, A.; Samuelov, Liat; Malchin, Natalia; Grafi-Cohen, Meital; Sprecher, Eli

doi:10.1111/ced.13324

Cited by 13 publications

(12 citation statements)

References 11 publications

(39 reference statements)

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“…Simultaneously, P8 at the age of 12‐year‐old with a mutation c.467G>A near c.466C>T presented severe hyperkeratosis as well as focal mild yellow PPK, localized to pressure area. Previously, neither EI caused by the recurrent mutation c.466C>T/c.467G>A nor recessive KRT10 associated EI cases showed the PPK phenotype . The underlying cause for the heterophany may be related to genetic/epigenetic factors, or that previous patients were relatively younger in the stage of blistering skin phenotype or in early stage of “phenotypic shift”.…”

Section: Discussionmentioning

confidence: 99%

Next‐generation sequencing through multi‐gene panel testing for diagnosis of hereditary ichthyosis in Chinese

Cheng

Liang

et al. 2020

Clinical Genetics

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Inherited ichthyoses are a heterogeneous group of rare disorders related to over 40 genes. To identify underlying molecular causes in inherited ichthyosis among Chinese and to correlate genotype and phenotype, 35 probands clinically diagnosed inherited ichthyosis, except ichthyosis vulgaris and X-linked ichthyosis, were included in our study. Molecular analysis was performed using next-generation sequencing (NGS) through multi-gene panel testing targeting all ichthyosis-related genes. Genetic variants causative for the ichthyosis were identified in 32 of 35 investigated patients.In all, 43 causative mutations across 12 genes were disclosed, including 16 novel variants. Thirteen keratinopathic ichthyosis, fourteen autosomal recessive congenital ichthyosis (ARCI) including one caused by mutations in SDR9C7, and five syndromic ichthyoses were confirmed. Four probands, with presumptive ARCI, turned out to be keratinopathic ichthyosis (2), neutral lipid storage disease (1), and Sjogren-Larsson syndrome (1), respectively. Next-generation technology has been demonstrated to be an effective tool in diagnosing inherited ichthyosis constituting a diverse group of cornification disorders. Our study further expands mutation spectrum and clinical phenotype associated with inherited ichthyosis in Chinese. K E Y W O R D S Chinese, congenital ichthyosis, mutation, next-generation sequence 1 | INTRODUCTION Inherited ichthyoses are genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis with a broad spectrum of skin manifestations. 1 Inherited ichthyoses have now been scientifically divided into two groups (nonsyndromic ichthyosis and syndromic forms) and multiple subgroups. 1 Identification of molecular cause is required and very important for clinical diagnosis and prognosis, genetic counseling, prenatal genetic diagnosis, optimized treatment and drug development. 2 However, over 40 genes have been related with ichthyoses.Conventional first-generation sequencing is obviously not suitable for efficient molecular analysis. Up to date, at least four studies have been succeeded in applying next-generation sequencing (NGS) technology in molecular analysis of inherited ichthyoses. 2,3 We aimed to identify the underlying mutations in inherited ichthyoses of Chinese descent using NGS methods.

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Section: Discussionmentioning

confidence: 99%

Next‐generation sequencing through multi‐gene panel testing for diagnosis of hereditary ichthyosis in Chinese

Cheng

Liang

et al. 2020

Clinical Genetics

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“…Mutations in the KRT1 and KRT10 genes induce clumping of the keratin intermediate filament (KIF) network in suprabasal keratinocytes, and cellular collapse. The mutations may also interfere with lamellar body secretion and therefore the lipid membrane formation, causing impaired barrier function [ 12 , 21 – 23 ].…”

Section: Molecular Pathology Of Ichthyosismentioning

confidence: 99%

New developments in the molecular treatment of ichthyosis: review of the literature

Joosten

Clabbers

Jonca

et al. 2022

Orphanet J Rare Dis

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Ichthyosis covers a wide spectrum of diseases affecting the cornification of the skin. In recent years, new advances in understanding the pathophysiology of ichthyosis have been made. This knowledge, combined with constant development of pathogenesis-based therapies, such as protein replacement therapy and gene therapy, are rather promising for patients with inherited skin diseases. Several ongoing trials are investigating the potency of these new approaches and various studies have already been published. Furthermore, a lot of case series report that biological therapeutics are effective treatment options, mainly for Netherton syndrome and autosomal recessive congenital ichthyosis. It is expected that some of these new therapies will prove their efficacy and will be incorporated in the treatment of ichthyosis.

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“…Epidermolytic ichthyosis (EI) is caused by mutations in genes encoding the keratins 1 and 10 (KRT1, KRT10) and is usually inherited in an autosomal‐dominant fashion. In rare instances, autosomal recessive inheritance has been described relying on a limited set of mutations mostly located in the central region of KRT10 . As the main clinical presentation, children with EI show fragile skin and exfoliation directly postnatally revealing underlying erythroderma (Figure C) accompanied by ichthyosiform erythroderma of varying severity in the following months of life.…”

Section: Differential Diagnoses Of the Red Scaly Babymentioning

confidence: 99%

“…In rare instances, autosomal recessive inheritance has been described relying on a limited set of mutations mostly located in the central region of KRT10. 12 As the main clinical presentation, children with EI show fragile skin and exfoliation directly postnatally revealing underlying erythroderma ( Figure 1C) accompanied by ichthyosiform erythroderma of varying severity in the following months of life. As a clue to the underlying mutation, thickened skin of the palms and soles (palmoplantar hyperkeratosis) is mainly observed in children with KRT1 and only very rarely with KRT10 mutations.…”

Section: Epidermolytic Ichthyosismentioning

confidence: 99%

Guidance for assessment of erythroderma in neonates and infants for the pediatric immunologist

Ott

2019

Pediatric Allergy Immunology

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Neonatal and infantile erythroderma (NIE) represents the common clinical phenotype of heterogeneous diseases ranging from benign and transient skin conditions to fatal multiorgan disorders. NIE regularly demands a comprehensive diagnostic workup in a multiprofessional setting, especially if newborns and young infants with the disease develop a failure to thrive and concomitant infectious, neurologic, or metabolic complications. By obtaining a detailed medical history and performing a thorough clinical examination, targeted diagnostic steps can be scheduled for most affected children. If NIE occurs in the early neonatal period, lesional skin biopsy and histology are often indicated. Likewise, if monogenic skin or immunologic diseases are suspected, genetic testing with customized panels of potentially underlying genes is mandatory. Of note, if acute symptoms such as severe infections, metabolic acidosis, or seizures occur, rapid microbiologic and metabolic investigations are warranted to rule out immunodeficiency and inborn errors of metabolism.

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Recessive epidermolytic ichthyosis results from loss of keratin 10 expression, regardless of the mutation location

Cited by 13 publications

References 11 publications

Next‐generation sequencing through multi‐gene panel testing for diagnosis of hereditary ichthyosis in Chinese

Next‐generation sequencing through multi‐gene panel testing for diagnosis of hereditary ichthyosis in Chinese

New developments in the molecular treatment of ichthyosis: review of the literature

Guidance for assessment of erythroderma in neonates and infants for the pediatric immunologist

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