OBJECTIVETo determine the molecular etiology for a Chinese pedigree affected with epidermolysis bullosa simplex (EBS).

METHODSTarget region sequencing using a hereditary epidermolysis bullosa capture array combined with Sanger sequencing and bioinformatics analysis were used. Mutation taster, PolyPhen-2, Provean, and SIFT software and NCBI online were employed to assess the pathogenicity and conservation of detected mutations. One hundred healthy unrelated individuals were used as controls.

RESULTSTarget region sequencing showed that the proband has carried a unreported heterozygous c.1234A>G (p.Ile412Val) mutation of the KRT14 gene, which was confirmed by Sanger sequencing in other 8 affected individuals but not among healthy members of the pedigree. Bioinformatics analysis indicated that the mutation is highly pathogenic. Remarkably, 3 members of the family (2 affected and 1 unaffected) have carried a heterozygous c.1237G>A (p.Ala413Thr) mutation of the KRT14 gene, which was collected in Human Gene Mutation Database (HGMD). Bioinformatics analysis indicated that the mutation may not be pathogenic. Both mutations were not detected among the 100 healthy controls.

CONCLUSIONThe novel c.1234A>G(p.Ile412Val) mutation of the KRT14 gene is probably responsible for the disease, while c.1237G>A (p.Ala413Thr) mutation of KRT14 gene may be a polymorphism. Compared with Sanger sequencing, target region capture sequencing is more efficient and can significantly reduce the cost of genetic testing for EBS.

Adult ; Amino Acid Sequence ; Case-Control Studies ; Epidermolysis Bullosa Simplex ; genetics ; Female ; Humans ; Keratin-14 ; genetics ; Male ; Mutation ; genetics ; Pedigree ; Young Adult

Epidermolysis bullosa simplex (EBS), an inherited genetic disorder, is most often caused by a dominant-negative mutation in either the keratin 5 (KRT5) or the keratin 14 (KRT14) gene. These keratin mutants result in a weakened cytoskeleton and cause extensive cytolysis. It is important to analyze the KRT5 or KRT14 genes of the patient and their family members by mutational analysis in order to identify genetic defects as well as the need for genetic counseling. In this study, we present a 5-year-old Korean boy who had been developing blisters and erosions on the palms of his hands and soles of his feet since infancy. In addition, while his younger sister and father showed similar clinical manifestation, his mother did not. The patient was diagnosed with EBS based on clinical manifestation, which is characterized by the presence of blisters restricted to the palms and soles, histological findings, and mutational analysis. Mutational analysis of the patient's DNA revealed a thymine-to-cytosine transition at codon 608 in the KRT-5 gene, resulting in a leucine-to-proline substitution in the keratin 5 protein. The same mutation was identified in the paternal, but not maternal, DNA. Here, we report a case of Weber-Cockayne type EBS with vesicles and bullae restricted to the palms and soles with a novel, paternally inherited mutation in KRT5 gene (exon2, c.608T>C).
Blister ; Child, Preschool ; Codon ; Cytoskeleton ; DNA ; Epidermolysis Bullosa Simplex* ; Fathers ; Foot ; Genetic Counseling ; Hand ; Humans ; Keratin-14 ; Keratin-5* ; Male ; Mothers ; Siblings

The other generalized type of epidermolysis bullosa simplex (EBS) is a genetic blistering skin disease, caused by a mutation of the genes encoding keratin 5 and 14. EBS starts at birth and is characterized by generalized blisters following a minor trauma that heals with hyperpigmentation. A 19-year-old man presented with 19-year history of multiple erythematous vesicles in a herpetiform arrangement on the trunk, axilla, and thigh with post-inflammatory hyper-pigmentations. On light and electron microscopy, the biopsy specimen showed intraepidermal blisters that formed within the basal keratinocyte. The serum from a patient with bullous pemphigoid antibody and laminin 5 antibody showed the linear deposition at the floor of the blister on immunofluorescence mapping study. On the basis of our clinical, microscopic, and immunofluorescence findings, we diagnosed the patient as having a generalized type of EBS. Herein, we report on an interesting case of the other generalized type of EBS.
Axilla ; Biopsy ; Blister ; Cell Adhesion Molecules ; Epidermolysis Bullosa ; Epidermolysis Bullosa Simplex ; Floors and Floorcoverings ; Fluorescent Antibody Technique ; Humans ; Hyperpigmentation ; Keratin-5 ; Keratinocytes ; Laminin ; Light ; Methylmethacrylates ; Microscopy, Electron ; Parturition ; Pemphigoid, Bullous ; Polystyrenes ; Skin Diseases ; Thigh

Epidermolysis bullosa (EB) is a rare genetic disease that is known for continuous skin blistering caused by minor trauma. The skin blisters and bullae that develop often cause skin defects. There is no definitive treatment for EB, only symptomatic relief. We report our experience with cultured allogenic keratinocyte grafting in a newborn patient with EB simplex who had unhealed raw surfaces and was not a skin grafting candidate. The skin lesions of the patient were covered with cultured allogenic keratinocyte grafts and re-epithelialized quickly with no scarring. Allogenic keratinocyte grafting reduced pain and produced noticeable improvements in the unhealed wounds. We think that allogenic keratinocyte grafting can play an important role in the management of patients with EB simplex.
Blister ; Cicatrix ; Epidermolysis Bullosa ; Epidermolysis Bullosa Simplex ; Humans ; Infant, Newborn ; Keratinocytes ; Methylmethacrylates ; Polystyrenes ; Skin ; Skin Transplantation ; Transplants

OBJECTIVETo identify keratin 5 (K5) and keratin 14 (K14) gene mutations in a family affected with epidermolysis bullosa simplex with mottled pigmentation.

METHODSGenomic DNA was extracted from peripheral blood samples obtained from eleven patients from the family and controls. All the exons of K5 and K14 genes were amplified using polymerase chain reaction (PCR) and directly sequenced.

RESULTSBy DNA sequence analysis, a missense mutation in K5 gene (c.237C>T) was detected. The same mutation was not found in non-affected members from the family and normal controls.

CONCLUSIONMutation in K5 gene (c.237C>T) may be responsible for the development of disease in this family.

Base Sequence ; DNA Mutational Analysis ; Epidermolysis Bullosa Simplex ; genetics ; pathology ; Exons ; Female ; Humans ; Hyperpigmentation ; genetics ; pathology ; Keratin-14 ; genetics ; Keratin-5 ; genetics ; Male ; Mutation ; Pedigree ; Sequence Analysis, DNA

Dystrophic epidermolysis bullosa is a rare, chronic non-inflammatory bullous disease with a hereditary pattern of occurrence, and this disease easily produces bullae that heal with scarring and milium formation. A 13-month-old female baby was brought to the department of dermatology with multiple variable sized bullae and erythematous to dark brownish patches and crusts on both her feet. The histopathologic findings showed subepidermal non-inflammatory blisters and the electron microscopic findings showed vacuolization of the sublamina densa and broken anchoring fibrils. On the basis of the clinical and microscopic findings, she was diagnosed as having dominant dystrophic epidermolysis bullosa. We report here on a case of dominant dystrophic epidermolysis bullosa with the clinical, histological and electron microscopic findings, as well as the family history of the patient.
Blister ; Cicatrix ; Dermatology ; Electrons ; Epidermolysis Bullosa Dystrophica ; Epidermolysis Bullosa Simplex ; Female ; Foot ; Humans ; Infant

Epidermolysis bullosa simplex (EBS), characterized by a cleavage plane through basal keratinocytes, is caused by a mutation of the genes encoding keratin 5 and 14. It is often regarded as the least severe form of Epidermolysis bullosa. In 1886, Koebner described the seasonal blisterings predominantly on the palms and soles but occurring on the other sites of friction with clothes as well. His name is often used to describe EBS with the generalized blisterings. We have experienced a case of Koebner variant of EBS in a two-day old male neonate whose father had the same EBS. Hereby, we report his clinical, histopathological findings with a brief review of the literature.
Blister ; Epidermolysis Bullosa Simplex* ; Epidermolysis Bullosa* ; Fathers ; Friction ; Humans ; Infant, Newborn ; Keratin-5 ; Keratinocytes ; Male ; Seasons

We report a case of epidermolysis bullosa simplex, Dowling-Meara type (EBS-DM), which was associated with congenital pyloric atresia (PA) and various urologic abnormalities, a diagnosis confirmed by immunofluorescence mapping and electron microscopic findings. Immunofluorescent mapping showed the serum from a patient with bullous pemphigoid faintly binding to the floor of the blister, and monoclonal antibodies against type IV and VII collagens were also stained on the floor of the blister. Electron microscopy showed epidermolytic cleavage and prominent clumping of tonofilaments in the basal and suprabasal keratinocytes. An abdominal radiograph and barium swallow showed a complete obstruction at the pyloric channel level. The widespread bullae healed without any scar formation and the bullae formation was localized on the extremities after 3 months of age without any specific treatment. Multiple urologic abnormalities such as bilateral hydronephrosis, hydroureter and a distended bladder with trabeculation were observed at 12 months of age. Currently, with the patient at 4 years of age, bullae still appear on the hands and feet and nail shedding can be observed. The patient's father, a paternal uncle and a paternal aunt had had similar bullous eruptions in infancy, all of which had improved spontaneously by the age of one.
Case Report ; Collagen/metabolism ; Epidermolysis Bullosa Simplex/pathology ; Epidermolysis Bullosa Simplex/metabolism ; Epidermolysis Bullosa Simplex/complications* ; Human ; Infant, Newborn ; Male ; Pylorus*/radiography ; Stomach Diseases/radiography ; Stomach Diseases/complications* ; Urologic Diseases/congenital* ; Urologic Diseases/complications*

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare subtype of EBS and characterized by blistering of the skin, mottled pigmentation, and palmoplantar hyperkeratosis. We report a 3-year-old boy with mottled pigmentation on the posterior neck, flank, buttock, and extremities, blisters on palm, and skin-colored keratotic papules on the hands and feet. He had had a history of blistering on his calves. His mother has similar skin lesions to her son's.
Blister ; Buttocks ; Child, Preschool ; Epidermolysis Bullosa Simplex* ; Epidermolysis Bullosa* ; Extremities ; Foot ; Hand ; Humans ; Male ; Mothers ; Neck ; Pigmentation* ; Skin

The Dowling-Meara type of epidermolysis bullosa simplex is a rare genodermatosis transmitted by autosomal dominant pattern. It starts during the first 3 months of life and is characterized by generalized bullae in a herpetiform pattern. We report two cases of Dowling-Meara type of epidermolysis bullosa simplex. The first case is an 18-year-old male patient who showed bullae in a herpetiform arrangement on the dorsa of both hands, forearms, and trunk, hyperkeratosis on the palms and soles, postinflammatory hypo- and hyperpigmentations, and dystrophy of finger and toe nails. The second case is a 1-month-old boy who showed multiple bullae in a herpetiform and confluent arrangement scattered on the whole body, particularly on the dorsa of both feet and hands. Microscopically and electro-microscopically, two cases all showed intraepidermal blisters formed within the basal keratinocyte in association with clumping of the tonofilaments and cytolysis of the basal cells.
Adolescent ; Blister ; Epidermolysis Bullosa Simplex* ; Epidermolysis Bullosa* ; Fingers ; Foot ; Forearm ; Hand ; Humans ; Infant, Newborn ; Intermediate Filaments ; Keratinocytes ; Male ; Toes