Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex

García, Marta; Santiago, Juan Luis; Terrón, Ana; Hernández‐Martín, Ángela; Vicente, A.; Fortuny, Clàudia; Lucas, R. de; López, J.C.; Cuadrado-Corrales, Natividad; Holguín, Almudena; Illera, Nuria; Duarte, Blanca; Sánchez-Jimeno, C.; Llames, Sara; García, Eva; Ayuso, Carmen; Martínez-Santamaría, Lucía; Castiglia, Daniele; Luca, Naomi De; Torrelo, Antonio; Mechan, D.; Baty, D.; Zambruno, Giovanna; Escámez, M.J.; Río, Marcela Del

doi:10.1111/j.1365-2133.2011.10428.x

Cited by 23 publications

(23 citation statements)

References 53 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The reticulated pattern of erythema, pigmentation, or both observed in these patients appears distinct and perhaps pathognomonic and is also noted by Komori et al in a recent report. It is different from the pigmentation observed in EBS with mottled pigmentation (EBS‐MP), a condition due to different mutations in K5 (p.Pro25Leu, p.Gly138Glu, p.[Ile140AsnfsX0]+[Asp328His], p.Gly550AlafsX77), K14 (p.Met119Thr, p.Ile373GlufsX53), and EXPH5 encoding exophilin‐5 . The condition is described as mottled pigmentation that may or may not be related to healing of blisters plus punctate palmoplantar keratoderma and onychodystrophy .…”

Section: Discussionmentioning

confidence: 92%

“…The condition is described as mottled pigmentation that may or may not be related to healing of blisters plus punctate palmoplantar keratoderma and onychodystrophy . Mutations in the V1 domain of the nonhelical head domain of K5 have been found in most cases of EBS‐MP . It is unclear why this mutation results in this unique clinical phenotype, though research done by Irvine et al indicates that the nonhelical head domain of K5 may be implicated in melanosome transport.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Epidermolysis bullosa simplex–generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype‐phenotype correlation and in silico modeling analysis

Lalor¹,

Titeux

Palisson

et al. 2018

Pediatric Dermatology

View full text Add to dashboard Cite

Background/Objectives Epidermolysis bullosa is a group of diseases caused by mutations in skin structural proteins. Availability of genetic sequencing makes identification of causative mutations easier, and genotype‐phenotype description and correlation are important. We describe six patients with a keratin 5 mutation resulting in a glutamic acid to lysine substitution at position 477 (p.Glu477Lys) who have a distinctive, severe and sometimes fatal phenotype. We also perform in silico modeling to show protein structural changes resulting in instability. Methods In this case series, we collected clinical data from six patients with this mutation identified from their national or local epidermolysis bullosa databases. We performed in silico modeling of the keratin 5‐keratin 14 coil 2B complex using CCBuilder and rendered with Pymol (Schrodinger, LLC, New York, NY). Results Features include aplasia cutis congenita, generalized blistering, palmoplantar keratoderma, onychodystrophy, airway and developmental abnormalities, and a distinctive reticulated skin pattern. Our in silico model of the keratin 5 p.Glu477Lys mutation predicts conformational change and modification of the surface charge of the keratin heterodimer, severely impairing filament stability. Conclusions Early recognition of the features of this genotype will improve care. In silico analysis of mutated keratin structures provides useful insights into structural instability.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Epidermolysis bullosa simplex–generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype‐phenotype correlation and in silico modeling analysis

Lalor¹,

Titeux

Palisson

et al. 2018

Pediatric Dermatology

View full text Add to dashboard Cite

show abstract

“…In EBS, skin fragility is thought to result from a defective assembly, growth and impaired stability of KIF (3,4). Mutations, usually missense substitutions, cluster in distinct domains of keratins and the severity of clinical manifestations seems to correlate with the localisation of these mutations (5)(6)(7). In the most severe form, the Dowling-Meara subtype (EBS-DM; MIM 131760), mutations are almost all located in the highly conserved ends of the alpha-helical rod domain of K5 and K14, whereas in the mildest variants, the 'localised EBS' (previously Weber-Cockayne; MIM 131800) and the 'EBS, other generalised' (previously Köebner; MIM 131900), mutations affect less conserved sequences of the alpha-helical rod domain, such as the linker regions.…”

mentioning

confidence: 99%

T-lymphocytes are Directly Involved in the Clinical Expression of Migratory Circinate Erythema in Epidermolysis Bullosa Simplex Patients

Castiglia¹,

Hachem²,

Diociaiuti³

et al. 2014

Acta Derm Venerol

View full text Add to dashboard Cite

Epidermolysis bullosa simplex with migratory circinate erythema (EBS-MCE) is a rare EBS subtype characterised by migratory blistering lesions that resolve with brownish pigmentation. It is caused by a recurrent readthrough mutation, c.1649delG, in the tail of keratin 5. Here, we report a child with EBS-MCE and investigated the immunologic mechanisms underlying the migratory lesions in this patient. A skin biopsy from the patient from an active border of an erythematous lesion was used for the immunohistochemical characterisation of the inflammatory infiltrate and for TUNEL assay to detect apoptotic cells. We found abundant CD4+ and CD8+ T lymphocytes infiltrating the papillary dermis and lining the dermal-epidermal junction. A number of these cells expressed the activation marker CD69. CD83+ dendritic cells were present both in the epidermis and papillary dermis. Finally, TUNEL staining showed apoptosis of basal and suprabasal keratinocytes. These findings suggest a critical role of the cellular immunity in determining the EBS-MCE phenotype.

show abstract

“…The severity of EBS is considered to depend on several factors, including the location of the mutations in KRT5 and KRT14, as well as biochemical differences of substituted amino acids . In example, other substitutions of 428 alanine reported so far: p.Ala428Thr and p.Ala428Val were observed in patients with localized and generalized intermediate subtypes, respectively . Furthermore, as it has been shown by Hovnanian in 1993, the heptad position of substituted amino acid in keratin helical domain is important with respect to its clinical significance .…”

Section: Discussionmentioning

confidence: 98%

A novel de novo mutation p.Ala428Asp in KRT5 gene as a cause of localized epidermolysis bullosa simplex

Stawczyk-Macieja

Wertheim–Tysarowska²,

Jakubowski

et al. 2019

Experimental Dermatology

View full text Add to dashboard Cite

Epidermolysis bullosa is a group of inherited blistering skin diseases resulting in most cases from missense mutations in KRT5 and KRT14 genes encoding the basal epidermal keratins 5 and 14. Here, we present a patient diagnosed with a localized subtype of epidermolysis bullosa simplex caused by a heterozygous mutation p.Ala428Asp in the KRT5 gene, that has not been previously identified. Moreover, a bioinformatic analysis of the novel mutation was performed, showing changes in the interaction network between the proteins. Identification of novel mutations and genotype‐phenotype correlations allow to better understanding of underlying pathophysiologic bases and is important for genetic counselling, patients’ management, and disease course prediction.

show abstract

Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex

Cited by 23 publications

References 53 publications

Epidermolysis bullosa simplex–generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype‐phenotype correlation and in silico modeling analysis

Epidermolysis bullosa simplex–generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype‐phenotype correlation and in silico modeling analysis

T-lymphocytes are Directly Involved in the Clinical Expression of Migratory Circinate Erythema in Epidermolysis Bullosa Simplex Patients

A novel de novo mutation p.Ala428Asp in KRT5 gene as a cause of localized epidermolysis bullosa simplex

Contact Info

Product

Resources

About