A5026895109- Vascular Malformations and Hemangiomas
- Genetic Syndromes and Imprinting
- Pulmonary Hypertension Research and Treatments
- Vascular Tumors and Angiosarcomas
- BRCA gene mutations in cancer
- Genomics and Rare Diseases
- RNA regulation and disease
- Soft tissue tumor case studies
- Congenital heart defects research
- Renal Diseases and Glomerulopathies
- PARP inhibition in cancer therapy
- Myasthenia Gravis and Thymoma
- Cardiovascular Conditions and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Bariatric Surgery and Outcomes
- Pharmacology and Obesity Treatment
- Genomic variations and chromosomal abnormalities
- Sexual Differentiation and Disorders
- Genetic and rare skin diseases.
- Histiocytic Disorders and Treatments
- Tuberous Sclerosis Complex Research
- Oral and gingival health research
- Immunodeficiency and Autoimmune Disorders
- Hedgehog Signaling Pathway Studies
University of Bari Aldo Moro
2017-2024
Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari
2020
Abstract Background PIK3CA-related overgrowth spectrum (PROS) refers to a group of rare disorders, caused by somatic activating mutations in PIK3CA, resulting abnormal PI3K-AKT-mTOR pathway signalling. Significant associated morbidity is frequently observed, and approved treatments are lacking. Miransertib (ARQ 092) novel, orally available, selective pan-AKT inhibitor with proven vitro efficacy. Following recent results the use AKT inhibitors Proteus syndrome (PS) AKT-mutant cancers, we...
Postzygotic mutations of the PIK3CA [phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha] gene constitutively activate PI3K/AKT/mTOR pathway in PIK3CA-related overgrowth spectrum (PROS) patients, causing congenital mosaic tissue that even multiple surgeries cannot solve. mTOR inhibitors are empirically tested and given for compassionate use these patients. PROS patients could be ideal candidates enrolment trials with PI3K/AKT inhibitors, considering "clean" cellular...
Postzygotic activating PIK3CA variants cause several phenotypes within the PIK3CA-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 an expanded cohort of 1007 PIK3CA-mutated patients, analysing our new data with previous literature to give a comprehensive picture.We performed ultradeep targeted next-generation sequencing (NGS)...
Abstract Proteus syndrome (PS) is an ultra‐rare disease characterized by progressive, disproportionate, segmental overgrowth caused a somatic gain‐of‐function mutation p.Glu17Lys in the oncogene AKT1 . The has high morbidity and mortality rates due to increased risk for patients develop cancer progressive overgrowth. A teenage patient with severe PS phenotype developed pelvic recurrence of low‐grade serous ovarian carcinoma (LGSOC). Taking into consideration, recent results use AKT...
Kaposiform hemangioendothelioma (KHE) is a rare locally aggressive mixed vascular tumor, with typical onset in early childhood and characterized by progressive angio- lymphangiogenesis. Its etiopathogenesis molecular bases are still unclear. Here, we report the first case of congenital KHE harboring PIK3CA mosaic pathogenic variant (c.323G > A, p.Arg108His) boy very subtle PIK3CA-related overgrowth spectrum (PROS) features. This finding provides insights into pathophysiology KHE, offering...
Activating pathogenic variants in PIK3CA gene usually occur at a mosaic status and underlie variety of segmental overgrowth phenotypes. Germline have been rarely reported, described total 12 patients with macrocephaly to date. Clinical prognostic features these germline not detail yet.Targeted deep sequencing by custom panel the 21 genes involved PI3K/AKT/mTOR pathway was performed 13-year-old boy physical overgrowth. analysis fibroblasts Western blot. The effects miransertib (AKT inhibitor)...
Smith-Kingsmore syndrome (SKS) is a rare autosomal dominant disorder caused by heterozygous germline activating pathogenic variants in mammalian target of rapamycin (MTOR) on chromosome 1p36. A few patients with disseminated mosaicism have been described so far and they seem to display different phenotype when compared cases. Here we report the sixth case mosaic MTOR variant, 7-year-old boy hemimegalencephaly, epilepsy, developmental delay, hypomelanosis Ito, lateralized overgrowth. Genetic...
Pathogenic variants in homologous recombination repair (HRR) genes other than BRCA1/2 have been associated with a high risk of ovarian cancer (OC). In current clinical practice, genetic testing is generally limited to BRCA1/2. Herein, we investigated the mutational status both and 5 HRR 69 unselected OC, evaluating advantage multigene panel everyday practice.We analyzed epithelial OC samples using an NGS custom pathways genes, beyond screening routine testing.Overall, 19 pathogenic (27.5%)...
Abstract Lateralized/segmental overgrowth disorders (LOs) encompass a heterogeneous group of congenital conditions with excessive body tissue growth. Documented molecular alterations in LOs mostly consist somatic variants genes the PI3KCA/AKT/mTOR pathway or chromosome band 11p15.5 imprinted region anomalies. In some cases, pathogenic RAS/MAPK have been reported. We present first case variant (T507K) PTPN11 causing LO phenotype characterized by severe lateralized overgrowth, vascular...
Congenital myasthenic syndromes (CMSs) are caused by mutations in genes that encode proteins involved the organization, maintenance, function, or modification of neuromuscular junction. Among these, collagenic tail endplate acetylcholinesterase protein (COLQ; MIM 603033) has a crucial role anchoring enzyme into synaptic basal lamina. Here, we report on first case patient with homozygous deletion affecting last exons COLQ gene CMS born to consanguineous parents Pakistani origin....
mTOR dysregulation has been described in pathological conditions, such as cardiovascular and overgrowth disorders. Here we report on the first case of a patient with complex congenital heart disease an interstitial duplication short arm chromosome 1, encompassing part gene. Our results suggest that intragenic microduplication might play role pathogenesis non-syndromic defects (CHDs) due to upregulation mTOR/Rictor consequently increased phosphorylation PI3K/AKT MEK/ERK signaling pathways...
BACKGROUNDLaminopathies are rare diseases, whose cardiac manifestations heterogeneous and, especially in their initial stage, similar to those of more common conditions, such as ischemic heart disease.Early diagnosis is essential, these conditions can first manifest themselves with sudden death.Electrical complications usually appear before structural complications; therefore, it important take into consideration genetic disorders for the differential brady and tachyarrhythmias, even when...
Abstract Background PIK3CA-related overgrowth spectrum (PROS) refers to a group of rare disorders, caused by somatic activating mutations in PIK3CA, resulting abnormal PI3K-AKT-mTOR pathway signalling. Significant associated morbidity is frequently observed, and approved treatments are lacking. Miransertib (ARQ 092) novel, orally available, selective pan-AKT inhibitor with proven vitro efficacy. Following recent results the use AKT inhibitors Proteus syndrome (PS) AKT-mutant cancers, we...