Total Synthesis of (±)-2-Debromohymenin via Gold-Catalyzed Intramolecular Alkyne Hydroarylation.

An intramolecular, gold-catalyzed alkyne hydroarylation results in the formation of the core pyrroloazepinone framework of the hymenin group of oroidin alkaloids. Elaboration of the cyclic adduct via C2-azidation, bromination of the pyrrole, and deprotection set the stage for global reduction with Mo(CO) resulting in the formation 2-debromohymenin.

Genomic imbalances defining novel intellectual disability associated loci.

Background: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID).

Results: We have detected CNVs in 30.

The Role of Copy Number Changes in Brain Abnormalities and Neurodevelopmental Disorders: Four New Cases and Literature Review.

Microdeletions at 1q43-q44 have been described as resulting in a clinically recognizable phenotype of intellectual disability (ID), facial dysmorphisms and microcephaly (MIC). In contrast, the reciprocal microduplications of 1q43-q44 region have been less frequently reported and patients showed a variable phenotype, including macrocephaly. Reports of a large number of patients with copy number variations involving this region highlighted the gene as a likely key player in head size anomalies.

Orthodontic Camouflage: A Treatment Option - A Clinical Case Report.

Unlabelled: Orthodontic camouflage provides an alternative treatment for angle III malocclusion since patients with limited economic resources cannot opt for orthognathic surgery, it being clear that correction will be achieved at the dental level and not at the bone complex.

Objective: To determine an alternative treatment for patients who do not have the possibility of having orthognathic surgery.

Clinical Case: A 13-year-old female patient, dolico facial biotype with slightly concave profile, with Class III Skeletal by mandibular prognathism, anterior crossbite, anterior diastema, and large mandibular body, molar class, and canine III.

The contribution of 7q33 copy number variations for intellectual disability.

Copy number variations (CNVs) at the 7q33 cytoband are very rarely described in the literature, and almost all of the cases comprise large deletions affecting more than just the q33 segment. We report seven patients (two families with two siblings and their affected mother and one unrelated patient) with neurodevelopmental delay associated with CNVs in 7q33 alone. All the patients presented mild to moderate intellectual disability (ID), dysmorphic features, and a behavioral phenotype characterized by aggressiveness and disinhibition.

Atypical haematological presentation in a case of polycythaemia vera with a new variant mutation detected in exon 12: c.1605G>T (p.Met535Ile).

One of the major genetic insights into the pathogenesis of polycythaemia vera included the identification of the somatic point gain-of-function mutations in Janus kinase 2 gene-first on exon 14, present in 95%-97% of the cases, and later on exon 12. In the literature, we can find some reported studies where different exon 12 mutations are identified. Unlike patients with mutation in exon 14, the mutation at exon 12 is not usually associated with an increase in the three haematopoietic series (erythrocytosis, leucocytosis and thrombocytosis).

Recurrent copy number variations as risk factors for neurodevelopmental disorders: critical overview and analysis of clinical implications.

Neurodevelopmental disorders (NDs) encompass a spectrum of neuropsychiatric manifestations. Chromosomal regions 1q21.1, 3q29, 15q11.

Instability of mRNA expression signatures of drug transporters in chronic myeloid leukemia patients resistant to imatinib.

Despite the success of imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), approximately 30% of patients are resistant to therapy, mostly due to unknown causes. To profile the expression signatures of drug transporters throughout IM therapy and correlate them with resistance, we quantified mRNA expression levels of the SLC22A12, ABCB1, ABCC1, ABCG2 and MVP genes in consecutive samples from peripheral blood or bone marrow of CML patients who were either responsive or resistant to IM. Additionally we identified and quantified BCR-ABL1 transcript variants and analyzed 1236T>C ABCB1 and 480G>C SLC22A1 polymorphisms.

DNA damage response in imatinib resistant chronic myeloid leukemia K562 cells.

Resistance to imatinib in patients with chronic myeloid leukemia can lead to advanced disease and blast crisis. Conventional chemotherapy with DNA damaging agents is then used, alone or in combination with other tyrosine kinase inhibitors (TKIs). Our aim was to assess whether imatinib resistant K562 cells were also resistant to DNA damaging agents.

Vascular Ehlers-Danlos syndrome: a case with fatal outcome.

A 13-year-old boy, born prematurely and hypotonic, from non-consanguineous healthy parents, was referred to our department because of easy bruising. A slightly extensible, thin and translucent skin, associated with dysmorphic facies, acrogeria, multiple ecchymoses, hypermobility of the small joints, dorsal kyphosis, genu valgum, flat feet, elongated upper limbs, and low muscle tone were all evident. A history of learning disability and bilateral inguinal hernia was present.