Autosomal recessive type of dystrophic epidermolysis bullosa with a novel variant in the COL7A1 gene.

Epidermolysis bullosa (EB) is an inherited skin condition whose hallmark is skin fragility caused by minimal trauma or friction. The dystrophic type of EB (DEB), accounting for 30% of all cases, is caused by mutations in the gene encoding type VII collagen α1 chain (COL7A1). It is inherited in an autosomal-dominant or autosomal-recessive manner. The clinical manifestations tend to be variable and frequently overlapping. Therefore, genetic testing is of great significance for establishing an exact genetic diagnosis. The present case study reports on a female patient with a clinical diagnosis of DEB, who had an inconclusive phenotype with no family history of DEB. Genetic analysis of the patient, via next-generation sequencing, revealed a compound heterozygous state for the COL7A1 gene. Segregation analysis revealed the parental origin of both variants-a missense variant [c.6022C>T p.(Arg2008Cys)] inherited from the father and a novel frameshift variant [c.3474del p.(Val1160Ter)] inherited from the mother. The established result assigned an exact genetic diagnosis and type of inheritance and allowed the personalization of the genetic counseling for this patient with regard to prognosis and future reproduction.

Relationship Between PD-L1, PD-1, CD8 and Clinicopathological Factors in Primary SCCs.

INTRODUCTION: Squamous cell carcinoma of the skin (SCCs) is the second most common skin cancer, with continuously increasing incidence. Programmed cell death ligand 1 (PD-L1), programmed cell death 1 receptor (PD-1), and CD8 expression in primary SCCs have not been described in many studies. OBJECTIVE: We investigated the association between PD-L1, PD-1, CD8, and clinicopathological prognostic factors for recurrence, metastasis, and mortality of SCCs. PATIENTS AND METHODS: Immunohistochemically stained sections of 100 primary SCCs divided into two groups according to diameter of the tumors (<20 mm and >20 mm) were assessed. Recombinant rabbit anti-PD-L1 antibody [SP142] - C-terminal, rabbit monoclonal anti-PD1 antibody [NAT105], and FLEX Mono Mo A-Hu CD8, cl C8/144B, RTU were used. RESULTS: We did not establish statistically significant differences between PD-L1, PD-1, CD8 expression, and high-risk clinicopathological features - tumor size >20 mm, depth >6 mm, poor tumor cell differentiation, perineural/lymphovascular invasion, low/absent lymphocyte stromal reaction. CONCLUSIONS: In primary SCCs, the expression of PD-L1, PD-1, and CD8 are not associated with high-risk clinicopathological factors. We suggest that these immunohistochemical markers are more significant in advanced cases and metastatic tissues.

Netherton Syndrome with a Novel Likely Pathogenic Variant c.420del (p.Ser141ProfsTer5) in SPINK5 Gene: A Case Report.

Introduction: Netherton syndrome (NS) is a rare autosomal recessive genodermatosis in the group of congenital ichthyosis. The clinical manifestations of the syndrome vary from a very mild clinical manifestation occurring with the picture of ichthyosis linearis circumflexa to exfoliative erythroderma. It can be fatal in the first days of a newborn's life due to dehydration, hypothermia, weight loss, respiratory infections, and sepsis. A specific anomaly of the hair trichorrexis invaginata is considered pathognomonic for the syndrome. Genetic testing of SPINK5 gene is key to confirming the diagnosis and starting early treatment. Case Presentation: We present a case report of NS in a 6-year-old boy who suffered from generalized erythroderma and desquamation of the skin from birth. The patient has atopic diathesis, recurrent skin infections, increased levels of IgE, and delayed physical development. Two genetic variants in SPINK5 gene with clinical significance were identified. The first detected variant is a nonsense mutation, predicted to cause loss of normal protein function either by protein truncation or by nonsense-mediated mRNA decay. The second variant is a likely pathogenic frameshift mutation that truncates the protein in 5 amino acids. The child was treated with acitretin, without satisfactory effect. Conclusion: The genetic variant we have described correlates with a severe clinical phenotype of NS. The second genetic variant of the SPINK5 gene, inherited from the father in our case, is novel and has never been published in the literature.