Epidermolysis bullosa simplex with mottled pigmentation: Clinical aspects and confirmation of the P24L mutation in theKRT5 gene in further patients

Moog, Ute; Die-Smulders, C.E.M. de; Scheffer, Hans; Vlies, Pieter van der; Henquet, C. J. M.; Jonkman, Marcel F.

doi:10.1002/(sici)1096-8628(19991008)86:4<376::aid-ajmg12>3.0.co;2-w

Cited by 23 publications

(29 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

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

“…All previously reported cases of EBS-MP examined demonstrated a heterozygous point mutation, P25L, in the non-helical V1 domain of keratin-5 (K5) molecule (Uttam et al, 1996;Irvine et al, 1997Irvine et al, , 2001Moog et al, 1999;Hamada et al, 2004). Recently, we encountered a Japanese female and her cousin affected with distal skin fragility, distribution of pigmented macules, toenail deformity, and histological findings of subepidermal blister with basal cell degeneration, compatible with EBS-MP.…”

mentioning

confidence: 96%

Clinical Heterogeneity of 1649delG Mutation in the Tail Domain of Keratin 5: A Japanese Family with Epidermolysis Bullosa Simplex with Mottled Pigmentation

Horiguchi¹,

Sawamura²,

Mori³

et al. 2005

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Twenty-five- and 22-y-old Japanese women, who are cousins, presented with distal skin fragility, widespread small, pigmented macules, and toenail deformity. Blisters occurred between the epidermis and the dermis with degeneration of the basal cells, suggesting epidermolysis bullosa simplex with mottled pigmentation (EBS-MP). Electron microscopy of the pigmented spots demonstrated vacuolization of basal cells as well as disturbed junctional structures and incontinence of pigmentation. Gene analysis resulted in detection of a heterozygous deletion of a guanine nucleotide in exon 9 at position 1649. P25L mutation was not detected in either case. It is possible that EBS-MP occurs not only based on the P25L mutation of the keratin 5 molecule, but also because of other types of mutations of epidermal keratin genes.

show abstract

“…The patient's presentation of blistering and pigmentation has to be differentiated from EBS with mottled pigmentation, Kindler syndrome, Naegeli syndrome and dyskeratosis congenita. 7 In EBS with mottled pigmentation, mucous membranes are generally spared and mottled pigmentation is not preceded by bullae. In addition, most patients with EBS with mottled pigmentation have been shown to carry a dominant missense mutation in the V1 domain of KRT5 (P25L).…”

Section: Resultsmentioning

confidence: 99%

A novel homozygous keratin 14 mutation in a patient with autosomal recessive epidermolysis bullosa simplex and squamous cell carcinoma of the tongue

Baek

Lee

et al. 2010

British Journal of Dermatology

View full text Add to dashboard Cite

Epidermolysis bullosa simplex (EBS) is a group of inherited skin disorders characterized by lysis of basal keratinocytes leading to the development of intraepidermal blisters from mild trauma. 1 EBS is known to be an autosomal dominant disorder; however, a few recessive cases have been reported. In EBS, the risk of cutaneous malignancy is not higher than in the normal population. 2 We present a patient who showed generalized blistering after minor trauma followed by brownish reticulated hyperpigmentation and squamous cell carcinoma of the tongue. We identified a novel homozygous KRT14 mutation (E392X) inherited in an autosomal recessive fashion. Case and methodsA 41-year-old Korean man was referred because of a lifelong tendency to develop blisters on his whole body in response to minimal trauma. Three months before admission, he detected a painful ulcerative mass on his lateral tongue and was diagnosed with squamous cell carcinoma. Clinical examination showed scattered blisters and superficial erosions on the sites of previous trivial trauma such as the trunk, extremities and palms ( Fig. 1a), generalized brownish reticulated patches ( Fig. 1b), punctuate keratoderma of the palms (Fig. 1c) and relatively diffuse keratoderma of the soles (Fig. 1d), hallux valgus deformities of the great toes, and dystrophic toenails (Fig. 1e). Hair and eyes were not affected. He was the son of unaffected parents of Korean origin without apparent consanguinity and he denied any of his relatives having a blistering disease. There was a history of frequent blistering of his tongue at the tumour site and a history of multiple dental caries. From early childhood, the patient developed palmoplantar punctuate hyperkeratosis and dystrophic toenails. Skin fragility had not lessened with age. All laboratory tests were negative or within normal limits. Histological examination revealed a subepidermal blister on staining with haematoxylin and eosin. Direct immunofluorescence was negative for IgG, IgM, IgA, C3, C4 and fibrinogen. Electron microscopy confirmed reduced keratin filaments and lysis of the basal keratinocytes. Mutation analysis was performed by polymerase chain reaction amplification of all the exons of the keratin 5 and keratin 14 genes from genomic DNA. Results and discussionA homozygous guanine to thymine transition at residue 1174 of the KRT14 genomic sequence was identified (Fig. 2). This nonsense mutation converts a glutamate residue at codon 392 to a stop codon. To exclude the possibility of selective amplification of one allele, we performed restriction fragment length polymorphism analysis with 50 unrelated controls and confirmed a homozygous mutation (Data S1; see Supporting information). However, due to the absence of parental DNA there is still a remote possibility of heterozygosity. The patient was diagnosed with autosomal recessive EBS with a novel homozygous KRT14 mutation.EBS is usually inherited in an autosomal dominant fashion, but there are several types which are inherited in an autosomal recessive fashion such...

show abstract

Epidermolysis bullosa simplex with mottled pigmentation: Clinical aspects and confirmation of the P24L mutation in theKRT5 gene in further patients

Cited by 23 publications

References 18 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

Clinical Heterogeneity of 1649delG Mutation in the Tail Domain of Keratin 5: A Japanese Family with Epidermolysis Bullosa Simplex with Mottled Pigmentation

A novel homozygous keratin 14 mutation in a patient with autosomal recessive epidermolysis bullosa simplex and squamous cell carcinoma of the tongue

Contact Info

Product

Resources

About