Genotypes and phenotypes heterogeneity in PIK3CA-related overgrowth spectrum and overlapping conditions: 150 novel patients and systematic review of 1007 patients with PIK3CA pathogenetic variants.

Background: Postzygotic activating variants cause several phenotypes within the -related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients and in an expanded cohort of 1007 mutated patients, analysing our new data with previous literature to give a comprehensive picture.

A Novel Genetic Variant in the WFS1 Gene in a Patient with Partial Uniparental Mero-Isodisomy of Chromosome 4.

Wolfram syndrome is a rare autosomal recessive disorder characterized by optic atrophy and diabetes mellitus. Wolfram syndrome type 1 (WFS1) is caused by bi-allelic pathogenic variations in the gene. We described the first case of WFS1 due to a maternal inherited mutation with uniparental mero-isodisomy of chromosome 4.

Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids.

The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK.

Association of autoimmune thyroiditis and celiac disease with Juvenile Polyposis due to 10q23.1q23.31 deletion: Potential role of PI3K/Akt pathway dysregulation.

Juvenile Polyposis (JP) is a rare hereditary condition characterized by diffuse hamartomatous gastrointestinal polyposis, associated with a significantly increased risk of neoplastic transformation. Most of the cases are caused by SMAD and BMPR1A mutations, while 10q23 microdeletions, encompassing both PTEN and BMPR1A oncogenes, are extremely rare, typically associated with more aggressive JP, and extraintestinal features overlapping with PTEN Hamartoma Tumor Syndrome. We present the first case of a young female with multiple autoimmune disorders (i.

Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study.

Background: Germline mutations in the STK11/LKB1 gene cause Peutz-Jeghers syndrome, an autosomal-dominantly inherited condition characterized by mucocutaneous pigmentation, hamartomatous gastrointestinal polyposis, and an increased risk for various malignancies. We here report the results of the first Italian collaborative study on Peutz-Jeghers syndrome.

Aims: To assess cancer risks in a large homogenous cohort of patients with Peutz-Jeghers syndrome, carrying, in large majority, an identified STK11/LKB1 mutation.

Breakpoint determination of 15 large deletions in Peutz-Jeghers subjects.

The Peutz-Jeghers Syndrome (PJS) is an autosomal dominant polyposis disorder with increased risk of multiple cancers. STK11/LKB1 (hereafter named STK11) germline mutations account for the large majority of PJS cases whereas large deletions account for about 30% of the cases. We report here the first thorough molecular characterization of 15 large deletions identified in a cohort of 51 clinically well-characterized PJS patients.

A homozygous frameshift mutation in the ESCO2 gene: evidence of intertissue and interindividual variation in Nmd efficiency.

Roberts syndrome (RS) is a rare disorder characterized by tetraphocomelia and several other clinical features. Cells from RS patients exhibit characteristic premature separation of heterochromatic region of many chromosomes and abnormalities in cell cycle. Mutations in the ESCO2 gene have recently been identified in 20 RS families.