The routine diagnosis of heritable skin and connective tissue disorders is complicated by the fact that in this group of disorders, clinical manifestations may result from genetic or phenotypic heterogeneity and the existence of new genes and/or novel disease subtypes. Autozygosity mapping (AM) has been proven to be a useful adjunct in the molecular diagnosis of homozygous autosomal recessive (AR) diseases. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using genomewide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases (84.7%) were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analyzed with an EB-targeted next-generation sequencing (NGS) panel. This approach identified mutations in five additional cases, initially undiagnosed due to presence of compound heterozygosity, deep intronic mutations, or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 out of 46 cases (95.7%) diagnosed genetically. The yield of 84.7% using AM-guided sequencing was remarkably similar to that of the independent use of our previously reported NGS targeted panel, in which potential causative variants were identified in 76 of 91 (83.5%) families with EB. Thus, AM is an expedient and cost efficient approach to identify mutated genes consanguineous families.

656 skin biopsies with positive direct immunofluorescence from the UK and overseas were studied over a 2-year period. The length of time biopsies had remained in Michel’s medium at pH 7.0 in various diseases (pemphigoid, pemphigus, linear IgA disease, epidermolysis bullosa acquisita, lupus erythematosus, vasculitis, amyloid, lichen planus and dermatitis herpetiformis) was analysed. We concluded that direct immunofluorescence remained positive at 6 months and that Michel’s medium is a reliable long-term maintenance medium for skin biopsies.

No therapeutic targets and molecular biomarkers are available in cervical cancer (CC) management. In other cancer types, micro-RNA-877-3p (miR-877-3p) has been associated with events relevant for CC development. Thus, we aimed to determine miR-877-3p role in CC. miR-877-3p levels were examined by quantitative-PCR in 117 cervical lesions and tumors. Effects on CC cell proliferation, migration, and invasion were evaluated upon anti-miR-877-3p transfection. miR-877-3p dependent molecular mechanism was comprehensively explored by proteomics, dual-luciferase reporter assay, western blot, and immunohistochemistry. Cervical tumors expressed higher miR-877-3p levels than benign lesions. miR-877-3p promoted CC cell migration and invasion, at least partly by modulating cytoskeletal protein folding through the chaperonin-containing T-complex protein 1 complex. Notably, miR-877-3p silencing synergized with paclitaxel. Interestingly, miR-877-3p downregulated the levels of an in silico-predicted target, ZNF177, whose expression and subcellular location significantly distinguished high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas of the cervix (SCCCs). Cytoplasmic ZNF177 was significantly associated with worse progression-free survival in SCCC. Our results suggest that: (i) miR-877-3p is a potential therapeutic target whose inhibition improves paclitaxel effects; (ii) the expression and location of its target ZNF177 could be diagnostic biomarkers between HSIL and SCCC; and (iii) cytoplasmic ZNF177 is a poor-prognosis biomarker in SCCC.

Conflicto de intereses: Los autores declaran no tener conflictos de intereses Imágenes: Los autores declaran haber obtenido las imágenes con el permiso de los pacientes Política de derechos y autoarchivo: se permite el autoarchivo de la versión post-print (SHERPA/RoMEO) Licencia CC BY-NC-ND. Licencia Creative Commons Atribución-NoComercial-SinDerivar 4.0 Internacional Universidad de Salamanca. Su comercialización está sujeta al permiso del editor MANIFESTACIONES CLÍNICAS DEL SÍNDROME DE RAMSAY-HUNT EN UNA SERIE DE 20 CASOS RAMÍREZ-SALAS JE ET AL.

Conflicto de intereses: Los autores declaran no tener conflictos de intereses Imágenes: Los autores declaran haber obtenido las imágenes con el permiso de los pacientes Política de derechos y autoarchivo: se permite el autoarchivo de la versión post-print (SHERPA/RoMEO) Licencia CC BY-NC-ND. Licencia Creative Commons Atribución-NoComercial-SinDerivar 4.0 Internacional Universidad de Salamanca. Su comercialización está sujeta al permiso del editor PALABRAS CLAVE: vértigo visual; rehabilitación vestibular; habituación; equilibrio; dependencia visual; estabilidad postural.