Pathomechanisms of epidermolysis bullosa: Beyond structural proteins.

Epidermolysis bullosa (EB), a phenotypically and genetically heterogeneous disorder, has been linked to mutations in the genes encoding structural proteins that reinforce skin integrity via dermal-epidermal adhesion. Breakdowns in these adhesion mechanisms result in four different subtypes of EB classified on the basis of the level of tissue separation within the cutaneous basement membrane zone (BMZ). Mutations in as many as 17 distinct genes that encode structural proteins in the BMZ have been linked to EB. Despite the clinical and histopathological confirmation of EB, many cases remain genetically unsolved. Technical advancements in next-generation sequencing have paved the way for the identification of genes involved in the pathophysiology of EB. Structural proteins have long been identified as the candidate molecules altered in EB, however, recently non-structural proteins, encoded for example by PLOD3, USB1, EXPH5, and KLHL24, involved in enzymatic modification or migration of structural proteins have been implicated. In this overview, we discuss recent work regarding these proteins vis-à-vis their function, associated clinical manifestations, and involvement in the pathogenesis of EB.

A Novel Mutation in Junctional Plakoglobin Causing Lethal Congenital Epidermolysis Bullosa.

We report a case of neonatal generalized erythema and epidermolysis resulting from a novel mutation in the junctional plakoglobin gene causing truncation of the plakoglobin protein. Expedited genetic testing enabled diagnosis while the patient was in the neonatal intensive care unit, providing valuable information for the clinicians and family.

Dermatosparaxia em um ovino: achados clínicos, anatomopatológicos e moleculares / Dermatosparaxis in a sheep: clinical, anatomopathological, and molecular findings

Background: Dermatosparaxis is an autosomal recessive genetic disease that affects the connective tissue of animals. Collagen proteins form fibrillar structures that provide strength and structure to the extracellular matrix of tissues and organs in the body. Therefore, changes in collagen synthesis result in hyperextensibility and skin fragility. Similar to dermatosparaxis in animals, some cases of Ehlers-Danlos syndrome type VIIC have been reported in humans. The objective of this study was to describe the clinical, anatomopathological, and molecular findings of a case of dermatosparaxis in a sheep bred by crossing the Santa Inês and White Dorper breeds. Case: A case of dermatosparaxis was reported in a 20-day-old female sheep, a cross between the Santa Inês and White Dorper breeds. The sheep exhibited hyperextensibility of the skin with minimal tension and increased joint volume shortly after birth. Because of clinical worsening and the poor prognosis of the disease, the owners opted for euthanasia. The necropsy revealed large ulcerated areas in several parts of the body, including the cervical, sternal, scapular, and thoracic regions, and the inner and outer thighs. The skin was extremely easy to be removed during the necropsy and the use of a scalpel was not necessary. Extensive areas of hemorrhage were observed in the subcutaneous tissue and small intestine. The histopathological findings of the skin lesions evidenced the presence of dermatosparaxis, particularly regarding the disorganization of collagen fibers. The tests involving Masson’s trichrome staining, picrosirius red staining, and Gomori’s trichrome staining under polarized light evidence of collagen fiber dysplasia.Discussion: The diagnosis of dermatosparaxis in this study was based on clinical, anatomopathological, and molecular analysis. Molecular diagnosis was confirmed by identification of SNP c.421G>T on the ADAMTS2 gene in both the mother and the sheep under study...

Dermatosparaxia em um ovino: achados clínicos, anatomopatológicos e moleculares / Dermatosparaxis in a sheep: clinical, anatomopathological, and molecular findings

Background: Dermatosparaxis is an autosomal recessive genetic disease that affects the connective tissue of animals. Collagen proteins form fibrillar structures that provide strength and structure to the extracellular matrix of tissues and organs in the body. Therefore, changes in collagen synthesis result in hyperextensibility and skin fragility. Similar to dermatosparaxis in animals, some cases of Ehlers-Danlos syndrome type VIIC have been reported in humans. The objective of this study was to describe the clinical, anatomopathological, and molecular findings of a case of dermatosparaxis in a sheep bred by crossing the Santa Inês and White Dorper breeds. Case: A case of dermatosparaxis was reported in a 20-day-old female sheep, a cross between the Santa Inês and White Dorper breeds. The sheep exhibited hyperextensibility of the skin with minimal tension and increased joint volume shortly after birth. Because of clinical worsening and the poor prognosis of the disease, the owners opted for euthanasia. The necropsy revealed large ulcerated areas in several parts of the body, including the cervical, sternal, scapular, and thoracic regions, and the inner and outer thighs. The skin was extremely easy to be removed during the necropsy and the use of a scalpel was not necessary. Extensive areas of hemorrhage were observed in the subcutaneous tissue and small intestine. The histopathological findings of the skin lesions evidenced the presence of dermatosparaxis, particularly regarding the disorganization of collagen fibers. The tests involving Massons trichrome staining, picrosirius red staining, and Gomoris trichrome staining under polarized light evidence of collagen fiber dysplasia.Discussion: The diagnosis of dermatosparaxis in this study was based on clinical, anatomopathological, and molecular analysis. Molecular diagnosis was confirmed by identification of SNP c.421G>T on the ADAMTS2 gene in both the mother and the sheep under study...(AU)

A Kindler syndrome-associated squamous cell carcinoma treated with radiotherapy.

Kindler syndrome1, 2 is a genetic disorder mainly characterized by increased skin fragility and photosensitivity,3, 4 making the use of treatments based on radiation difficult or even prohibited. Thus, cases reporting Kindler syndrome patients treated with radiotherapy are rare. In this study, we report clinical outcomes and care provided for a rare case of a Kindler syndrome patient submitted to radiotherapy. Diagnosed with squamous cell carcinoma involving the buccal mucosa, the patient was exclusively treated with radiotherapy, with 70 Gy delivered on the PTV with the Volumetric Modulated Arc technique. The patient's reaction regarding control of the lesion is relevant compared to patients not affected by the syndrome. We noticed acute reactions of the skin and buccal mucosa after few radiotherapy sessions, followed by a fast reduction in the tumor volume. The efficacy of radiotherapy along with multidisciplinary actions allowed treatment continuity, leading to a complete control of the lesion and life quality improvement and showed that the use of radiotherapy on Kindler syndrome patients is possible.