INTRODUCTION The ATP6AP1 gene encodes for ATPase H+ transporting protein. ATP6AP1 gene mutations are associated with congenital disorders of glycosylation (CDG) and can affect multiple organ system. Descriptions of postnatal phenotype include immunodeficiency, hepatopathy and cognitive impairment. No prenatal phenotype of these gene mutations has been described to date. CASE This is a description of the prenatal workup of an infant diagnosed with a X-linked ATP6AP1 gene mutation. First trimester ultrasound demonstrated a thickened nuchal translucency measured at 3.27 mm and dysmorphic spinal canal, corresponding to kyphoscoliosis finding postnatally. Findings from amniocentesis at 15 weeks included elevated amniotic fluid alpha-fetoprotein (AF-AFP) and positive acetylcholinesterase (AchE). Dilation of the aortic arch was seen on fetal echocardiogram at 20 weeks. Throughout the second trimester, a rim of fluid collection was seen under the skin covering the thoracic and lumbar fetal spine, consistent with a large Aplasia Cutis below the right scapula present at birth. CONCLUSION To our knowledge, this is the first description of prenatal phenotype of an X-linked ATP6AP1 gene mutation, and the association of this gene mutation with increased NT, elevated AF-AFP and AchE and Aplasia Cutis Congenita. This variant was submitted to ClinVar public database, submission ID SUB6537411. The application of next-generation sequencing to fetal pathology has proved to increase the diagnostic yield in fetuses with abnormal ultrasounds. We retrospectively reviewed genetic data of 30 selected cases studied through targeted resequencing of OMIM genes. In our experience, clinical data proved to be essential to support diagnostic reasoning and enhance variants' assessment. The molecular diagnosis was reached in 19/30 (63%) cases.  https://www.selleckchem.com/products/Chlorogenic-acid.html  Only in 7/19 cases the molecular diagnosis confirmed the initial diagnostic hypothesis, showing the relevance of the genotype-first approach. According to the genotype-phenotype correlation, we were able to divide the solved cases into three groups i) the correlation is well established but it was missed due to lack of specificity, unusual presentation or recent description; ii) the clinical presentation is much more severe than currently known for the underlying condition; iii) the correlation does not recapitulate the entire phenotype, possibly due to the fetal presentation or multiple coexisting conditions. Moreover, we found a higher proportion of recessive diagnosis in abnormal fetuses compared to cohorts of individuals with developmental delay. Our findings suggest that fetal pathology may be enriched in rare alleles and/or in unusual combinations, counter-selected in postnatal genomes and thus contributing to both phenotypic extremeness and atypical presentation. INTRODUCTION Male Breast Cancer (MBC) is a rare disease, about 1% of all breast cancers worldwide and less than 1% of cancers occurring in men. The bilateral male breast cancer (bMBC) is extremely rare. Germline mutations of BRCA1/BRCA2 genes are associated with a significantly increased risk of cancer in MBC; the role of PALB2 remains to be clarified. Our main goal was to provide contribution on characterization of BRCA1/BRCA2 and PALB2 mutations in MBC patients. METHODS We observed 28 MBC cases; one of them was a bMBC. Screening for BRCA1, BRCA2 and PALB2 genes was performed on all 28 MBC patients. Mutational analysis was extended to family members of mutated patients. RESULTS In our study, the MBC incidence was 5.2% and for bMBC was 3.6%. Mutation analysis showed pathogenic mutations in 11/28 (39.3%) patients; 2/28 (7.1%) displayed a mutation in BRCA1, 8/28 (28.6%) in BRCA2 and 1/28 (3.6%) in PALB2. Out of 11 mutated patients, one (9.1%) reported a double mutation in BRCA2. Personal history of other cancers was reported in 2/28 (7.1%) patients affected by bladder cancer. A first/second degree family history of breast/ovarian and other cancers occurred in 23/28 (82.1%) patients. CONCLUSION Our findings indicate BRCA2 as the main MBC susceptibility gene and describe an increased risk of bMBC and bladder cancer in mutated patients. The identification of mutations in MBC susceptibility genes supports the usage of oncology prevention programs in affected patients and their relatives carrying the mutation. INTRODUCTION Cowden syndrome is a cancer predisposition syndrome caused by pathogenic variants in PTEN. The affected patients possess an increased risk of breast, thyroid, renal, colorectal, endometrial cancers as well as malignant melanoma. Thus prophylactic surveillance and follow up is crucial for these patients. METHODS A review of the literature including existing guidelines from the years 1996 until 2017 was carried out. In total, 2078 scientific papers were identified through database searches on Cowden syndrome. Among these, 11 manuscripts were included based on scientific relevance and quality. Expert consensus was reached to define management guidelines. RESULTS The literature revealed a high risk of cancer in specific organs for patients diagnosed with Cowden Syndrome. Alternative management guidelines were proposed and discussed. CONCLUSIONS Here we propose a revised set of management guidelines for patients with Cowden syndrome in Denmark to address the increased risk of various cancer types. Chemotherapeutic strategy has been widely used for treating malignance by targeting irregular expressed or mutant proteins with small molecular inhibitors (SMIs) or monoclonal antibodies (mAbs). However, most intracellular proteins lack of active sites or antigens where SMIs or mAbs bind with, and are called as non-druggable targets for a long time. From the first year of this century, PROteolysis-TArgeting Chimeras (PROTACs) has emerged to be a promising approach for proteins, including those non-druggable ones, such as transcriptional factors and scaffold proteins. The first generation of peptide-based PROTACs adopts β-TrCP and VHL as E3 ligases, but the cellular permeability and chemical stability issues restrict their clinical application. The second generation of small molecule-based PROTACs adopts MDM2, VHL, IAPs and Cereblon as E3 ligases have been tensely studied. To date, the targets of PROTACs including those overexpressed oncogenic proteins such as ER, AR and BRDs, disease-relevant fusion proteins such as NPM/EML4-ALK and BCR-ABL, cancer-driven mutant proteins such as EGFR, kinases such as CDKs and RTKs.