Impact of NSD1 Alternative Transcripts in Actin Filament Formation and Cellular Division Pathways in Fibroblasts

Germline variants in the NSD1 gene are responsible for Sotos syndrome, while somatic variants promote neoplastic cell transformation. Our previous studies revealed three alternative RNA isoforms of NSD1 present in fibroblast cell lines (FBs): the canonical full transcript and 2 alternative transcripts, termed AT2 (NSD1 Δ5Δ7) and AT3 (NSD1 Δ19–23 at the 5′ end). The precise molecular pathways affected by each specific isoform of NSD1 are uncharacterized to date. To elucidate the role of these isoforms, their expression was suppressed by siRNA knockdown in FBs and protein expression and transcriptome data was explored. We demonstrate that one gene target of NSD1 isoform AT2 is ARP3 actin-related protein 3 homolog B (ACTR3B). We show that loss of both canonical NSD1 and AT2 isoforms impaired the ability of fibroblasts to regulate the actin cytoskeleton, and we observed that this caused selective loss of stress fibers. Our findings provide novel insights into NSD1 function by distinguishing isoform function and demonstrating an essential role of NSD1 in regulating the actin cytoskeleton and stress fiber formation in fibroblasts

Children and adults affected by Cri du Chat syndrome: Care's recommendations

Our objective is to collect data and information for a better care and follow up in Cri du Chat patients. We conducted a literature review in August 2017 and then discuss the outcomes within the ABC (Associazione Bambini Cri du Chat, Italian CdC families support group). A proposal for clinical, laboratory and imaging work up should be performed at various ages in CdC patients. Follow up and rehabilitation should continue lifelong as some improvements can be obtained also in older ages and not to lose acquired skills

Intervertebral disc and endplate cell characterisation highlights annulus fibrosus cells as the most promising for tissue-specific disc degeneration therapy

Degenerative processes of the intervertebral disc (IVD) and cartilaginous endplate lead to chronic spine pathologies. Several studies speculated on the intrinsic regenerative capacity of degenerated IVD related to the presence of local mesenchymal progenitors. However, a complete characterisation of the resident IVD cell populations, particularly that isolated from the endplate, is lacking. The purpose of the present study was to characterise the gene expression profiles of human nucleus pulposus (NPCs), annulus fibrosus (AFCs) and endplate (EPCs) cells, setting the basis for future studies aimed at identifying the most promising cells for regenerative purposes. Cells isolated from NP, AF and EP were analysed after in vitro expansion for their stemness ability, immunophenotype and gene profiles by large-scale microarray analysis. The three cell populations shared a similar clonogenic, adipogenic and osteogenic potential, as well as an immunophenotype with a pattern resembling that of mesenchymal stem cells. NPCs maintained the greatest chondrogenic potential and shared with EPCs the loss of proliferation capability during expansion. The largest number of selectively highly expressed stemness, chondrogenic/tissue-specific and surface genes was found in AFCs, thus representing the most promising source of tissue-specific expanded cells for the treatment of IVD degeneration

A Rare Case of Deletion in 2q24.1: Clinical Features and Response to Gh Hormone Treatment

Background: Chromosomal imbalances are often due to sub microscopic deletions or duplications not evidenced by conventional cytogenetic methods. Objective and hypotheses: CGH array can help in the diagnosis of severe short stature, associated with mental retardation and dysmorphisms. Method: We describe the clinical case of a 13.1-year-old girl, born at 35 weeks, from a triplets pregnancy. She was 127.5 cm (!K5 SDS), 33 kg (! K3 SDS); SPAN: 122 cm; PH2B2, bone age: 11 years; mild psychomotor delay, facial dysmorphism (malformed years with a low-set, microcephaly) and feet malformations (flexion deformities, broad halluces). Born SGA, with a growth velocity ! K3 SDS, a severe short stature she was a candidate to GH treatment. She started GH at the dosage of 0.035 mg/kg per day with a significant improvement of growth velocity. She had FSH, LH, TSH, fT4: in the normal range; low IGF-1 levels: 139 ng/ml (n.v. for age: 183–850). Results: CGH array evidenced a microdeletion of chromosome 2 (2q24.1), interesting genes UPP2, CCDC148, CCDC148-AS1, partially gene PKP4. MRI of CNS and pituitary revealed a small hypophysis with an intrasellar arachnoid cyst. After 11 months of GH treatment she was 134.8 cm (K3SDS), 37 kg; PH3B2. Conclusion: A few cases of deletion of 2q24 are reported in literature, and the association of low birth weight, growth delay, mental retardation, facial dysmorphism, cardiac malformations, feet and hands deformities is specific of this deletion. The mild phenotype of our patient could be explained by the small deletion (2q24.1). For this reason, it could be considered a continuous gene syndrome. At our knowledge this is the first case reported in the literature treated with GH and showing a satisfactory growth

Contenuto di cellule somatiche del latte ovino: effetti sulla composizione, sulle frazioni proteiche e sul contenuto di sali minerali

Aim of the research was to assess how two different somatic cell (SCC) levels (<250,000 cells/mL and> 250,000 cells/ mL) affect nutritional composition, protein fractions and mineral content of sheep milk. The samples were collected during two years from three different sheep farms. In each farm, by once samples per season, 11 comparisons were made between individual milks, one with low SCC (up to 250,000 cells/mL; CB) and one with high SCC (over 250,000 cells/mL; CE). Overall, CE milk had a lower content of lactose (4.05 vs 4.60 g/100g), casein (3.91 vs 4.28 g/100g), phosphorus (131.31 vs 138.81 mg/100g), calcium (157.28 vs 170.48 mg/100g) and magnesium (14.59 vs 15.30 mg/100g), compared to CB milk. Moreover, CE milk had a lower casein number (76.53 vs 79.03%) and higher ash (0.90 vs 0.87 g/100g) and chloride (103.57 vs 93.17 mg/100g) contents, compared to CB milk. In conclusion, for its higher casein, phosphorus, calcium and magnesium contents, CB milk was more suitable for cheese production than CE milk

A 12.4 Mb direct duplication in 19q12-q13 in a boy with cardiac and CNS malformations and developmental delay

The interstitial duplication of the long arm of chromosome 19 is a rare abnormality, characterized by developmental delay and dysmorphic features, also reported in association with cardiac, urinary, and CNS malformations. We describe a new case of de novo 19q12-q13. 2 duplication characterized by fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (CGH) and, by reviewing the data from previous articles, we report a tentative genotype/phenotype correlation. Four previously described cases showed the same or overlapping 19q duplications and shared with our patient common dysmorphisms, psychomotor retardation, and CNS malformations. The present description of a new case of 19q12-q13. 2 duplication with a molecular cytogenetic and genomic characterization adds further elements to the understanding of the impact of the genomic segment on the phenotype. © 2011 Institute of Plant Genetics, Polish Academy of Sciences, Poznan

The crucial role of FBXO28 in the pathogenesis of the 1q41q42 microdeletion syndrome

no abstract availabl