Mild phenotype of epidermolytic hyperkeratosis mimicking ichthyosis bullosa of Siemens is related to specific mutation in 2B domain of KRT1

Sung, Jae Yong; Oh, Seung Joon; Kim, Soo Chan

doi:10.1016/j.jdermsci.2013.03.001

Cited by 7 publications

(7 citation statements)

References 18 publications

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“…8 This large variation in phenotype can even occur in patients with the same mutation. For example, the mutation c.1434G>T, p.Glu478Asp in KRT1 has been reported previously in patients from Japan and Korea (16)(17)(18). Patients described in these publications showed a very mild phenotype and had similar clinicopathological features to SEI.…”

Section: Discussionmentioning

confidence: 76%

“…The mutation p.Glu478Asp does not lead to a change in side-chain polarity, in contrast to the mutations p.Glu478Gln and p.Glu478Lys, which change polarity and lead to more severe phenotypes. Sung et al (18) postulated that the polarity of the substituted amino acid can influence the phenotypic severity of EI. Indeed, patient P7, who carries the p.Glu478Asp mutation, showed a mild generalized ichthyosis.…”

Section: Discussionmentioning

confidence: 99%

“…In patient P23 the splice site mutation c.1374-1G>C, 1 http://www.medicaljournals.se/acta/content/?doi=10.2340/00015555-2299 2 The mutations c.558C>A, p.Asn186Lys (patient P1) and c.1459G>A, p.Glu487Lys (family 3 (patients P3-1, P3-2 and P3-3) and patient P4) have been described previously (12,13). 3 The mutations c.698C>T, p.Ser233Leu (14) in patient P6, c.1436T>C, p.Ile479Thr (15) in family 8 (P8-1, P8-2), c.1434G>T, p.Glu478Asp (16)(17)(18) in patient P7, c.1468G>A, p.Glu490Lys (7) in patient P9 and c.563A>G, p.Asn188Ser (19) in patient P5 have been described previously. 4 Six patients have the mutation c.467G>A, p.Arg156His (20) and 1 patient has the mutation c.467G>T, p.Arg156Leu (21).…”

Section: Congenital Reticular Ichthyosiform Erythrodermamentioning

confidence: 99%

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Expanding the Clinical and Genetic Spectrum of KRT1, KRT2 and KRT10 Mutations in Keratinopathic Ichthyosis

Hotz¹,

Oji²,

Bourrat³

et al. 2016

Acta Derm Venerol

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Twenty-six families with keratinopathic ichthyoses (epidermolytic ichthyosis, superficial epidermolytic ichthyosis or congenital reticular ichthyosiform erythroderma) were studied. Epidermolytic ichthyosis is caused by mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. In this study mutations were found in KRT1, KRT2 and KRT10, including 8 mutations that are novel pathogenic variants. We report here the first case of a patient with congenital reticular ichthyosiform erythroderma carrying a mutation in KRT10 that does not lead to an arginine-rich reading frame. Novel clinical features found in patients with congenital reticular ichthyosiform erythroderma are described, such as mental retardation, spasticity, facial dysmorphisms, symblepharon and malposition of the 4th toe.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Congenital Reticular Ichthyosiform Erythrodermamentioning

confidence: 99%

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Expanding the Clinical and Genetic Spectrum of KRT1, KRT2 and KRT10 Mutations in Keratinopathic Ichthyosis

Hotz¹,

Oji²,

Bourrat³

et al. 2016

Acta Derm Venerol

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“…To understand the reasons for filament collapse rather than cytotoxic aggregation in mild EI keratinocytes, we sought to study the K1-K10 polymer structure in wild-type (WT) and mutant states. However, such investigations were limited by the absence of a K1-K10 crystal structure (Sung et al, 2013). Capitalizing on the homology between keratin rod domains, we generated a computational model of K1-K10 using the K5-K14 crystal structure as a template (Lee et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Mutations Affecting Keratin 10 Surface-Exposed Residues Highlight the Structural Basis of Phenotypic Variation in Epidermolytic Ichthyosis

Mirza

Kumar

Craiglow

et al. 2015

Journal of Investigative Dermatology

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Epidermolytic ichthyosis (EI) due to KRT10 mutations is a rare, typically autosomal dominant, disorder characterized by generalized erythema and cutaneous blistering at birth followed by hyperkeratosis and less frequent blistering later in life. We identified two KRT10 mutations p.Q434del and p.R441P in subjects presenting with a mild EI phenotype. Both occur within the mutational "hot spot" of the keratin 10 (K10) 2B rod domain, adjacent to severe EI-associated mutations. p.Q434del and p.R441P formed collapsed K10 fibers rather than aggregates characteristic of severe EI KRT10 mutations such as p.R156C. Upon differentiation, keratinocytes from p.Q434del showed significantly lower apoptosis (P-value<0.01) compared with p.R156C as assessed by the TUNEL assay. Conversely, the mitotic index of the p.Q434del epidermis was significantly higher compared with that of p.R156C (P-value<0.01) as estimated by the Ki67 assay. Structural basis of EI phenotype variation was investigated by homology-based modeling of wild-type and mutant K1-K10 dimers. Both mild EI mutations were found to affect the surface-exposed residues of the K10 alpha helix coiled-coil and caused localized disorganization of the K1-K10 heterodimer. In contrast, adjacent severe EI mutations disrupt key intermolecular dimer interactions. Our findings provide structural insights into phenotypic variation in EI due to KRT10 mutations.

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“…However, specific mutations in 2B domain, which showed mild EI, were recently reported. 4,5 In KRT1, mutations in the elongated tail domain were reported in two EI cases, one showing a severe phenotype 6 and the other showing a mild phenotype. 7 Concerning the effects of KRT1 mutations in the elongated tail domain on the structure of that domain, eight of ten glycine loops in the tail domain were found to be conserved in the above-mentioned mild case.…”

Section: Editormentioning

confidence: 99%

A case of epidermolytic ichthyosis showing a very mild phenotype due to a novel tail extension mutation in KRT10

Kono

Fukai

Omura

et al. 2016

Acad Dermatol Venereol

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Mild phenotype of epidermolytic hyperkeratosis mimicking ichthyosis bullosa of Siemens is related to specific mutation in 2B domain of KRT1

Cited by 7 publications

References 18 publications

Expanding the Clinical and Genetic Spectrum of KRT1, KRT2 and KRT10 Mutations in Keratinopathic Ichthyosis

Expanding the Clinical and Genetic Spectrum of KRT1, KRT2 and KRT10 Mutations in Keratinopathic Ichthyosis

Mutations Affecting Keratin 10 Surface-Exposed Residues Highlight the Structural Basis of Phenotypic Variation in Epidermolytic Ichthyosis

A case of epidermolytic ichthyosis showing a very mild phenotype due to a novel tail extension mutation in KRT10

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