Chromoanagenesis of chromosome 22 in a subject with obesity and borderline cognitive performance.

Chromoanagenesis events consist of complex chromosome rearrangements with multiple breakpoints in one or few chromosomes. Mechanisms of chromoanagenesis are split into three major groups: chromothripsis, chromoanasynthesis and chromoplexy. This study aims to delineate a chromoanagenesis event at the level of chromosome 22 in an individual showing obesity and borderline cognitive performance as major disturbances.

Dystonic tremor and blepharospasm in a patient with deletion of 18q.

18q- Syndrome is a rare chromosomic syndrome where neurological involvement is scarcely described. Movement disorders are rare and only one case with dystonia was described. In our paper, we describe the second report of a patient with 18q- Syndrome, blepharospasm, and dystonic tremor of his right hand and hyperthyroidism instead of hypothyroidism.

Novel IGFALS mutations with predicted pathogenetic effects by the analysis of AlphaFold structure.

Purpose: According to the American College of Medical Genetics (ACMG) classification, variants of uncertain significance (VUS) are gene variations whose impact on the disease risk is not yet known. VUS, therefore, represent an unmet need for genetic counselling. Aim of the study is the use the AlphaFold artificial intelligence algorithm to predict the impact of novel mutations of the IGFALS gene, detected in a subject with short stature and initially classified as VUS according to the ACMG classification.

A novel de novo HDAC8 missense mutation causing Cornelia de Lange syndrome.

Background: Cornelia de Lange syndrome (CdLS) is a rare and clinically variable syndrome characterized by growth impairment, multi-organ anomalies, and a typical set of facial dysmorphisms. Here we describe a 2-year-old female child harboring a novel de novo missense variant in HDAC8, whose phenotypical score, according to the recent consensus on CdLS clinical diagnostic criteria, allowed the diagnosis of a non-classic CdLS.

Methods: Clinical exome sequencing was performed on the trio, identifying a de novo heterozygous variant in HDAC8 (NM_018486; c.

A paternally inherited 1.4 kb deletion of the 11p15.5 imprinting center 2 is associated with a mild familial Silver-Russell syndrome phenotype.

The Silver-Russell syndrome (SRS) is a rare disorder characterized by heterogeneous clinical features, including growth retardation, typical facial dysmorphisms, and body asymmetry. Genetic alterations causative of SRS mostly affect imprinted genes located on chromosomes 7 or 11. Hypomethylation of the Imprinting Center 1 (IC1) of the chromosome 11p15.

CACNA1C haploinsufficiency accounts for the common features of interstitial 12p13.33 deletion carriers.

We identified a de novo 44.7 Kb interstitial 12p13.33 micro-deletion that involves solely the first exon of the CACNA1C (MIM 114205), using microarray-based comparative genomic hybridization (aCGH).

Quantitative PCR evaluation of deletions/duplications identified by array CGH.

Genomic deletions/duplications detected by array comparative genomic hybridization (aCGH) should be confirmed by an independent technology. This approach allows also to test, at low cost, inheritance of the imbalance. In the present study we explored the use of quantitative PCR (qPCR) to confirm aCGH-detected potentially clinically relevant imbalances.

Genomic Deletion Involving the IMMP2L Gene in Two Cases of Autism Spectrum Disorder.

Mutations/deletions of the IMMP2L gene have been associated with different cognitive/behavioral disturbances, including autism spectrum disorders (ASD). The penetrance of these defects is not complete since they often are inherited from a healthy parent. Using array-CGH in a cohort of 37 ASD patients, we found 2 subjects harboring a deletion inside the IMMP2L gene.

Evaluation of somatic genomic imbalances in thyroid carcinomas of follicular origin by CGH-based approaches.

Application of distinct technologies of cancer genome analysis has provided important information for the molecular characterization of several human neoplasia, including follicular cell-derived thyroid carcinoma. Among them, comparative genomic hybridization (CGH)-based procedures have been extensively applied to evaluate genomic imbalances present in these tumours, obtaining data leading to an increase in the understanding of their complexity and diversity. In this review, after a brief overview of the most commonly used CGH-based technichs, we will describe the major results deriving from the most influential studies in the literature which used this approach to investigate the genomic aberrations of thyroid cancer cells.

Familial 5q12.3 Microdeletion: Evidence for a Locus Associated with Epilepsy.

The clinical use of array comparative genomic hybridization (array CGH) has allowed the identification of very rare deletion and duplication disorders, such as 5q12 deletion syndrome (OMIM 615668) described as a contiguous gene deletion syndrome of chromosome 5q12. Chromosome microdeletions including band 5q12 have rarely been reported and have been associated with different phenotypes showing postnatal growth restriction, intellectual disability, epileptic seizures, hyperactivity, and ocular abnormalities. In this study, we describe a family in which array-CGH analysis revealed the presence of an interstitial microdeletion spanning approximately 2.

Microdeletion 15q26.2qter and Microduplication 18q23 in a Patient with Prader-Willi-Like Syndrome: Clinical Findings.

The small interstitial deletion in the long arm of chromosome 15 causing Prader-Willi/Angelman syndrome is well known, whereas cases that report terminal deletions in 15q in association with the Prader-Willi-like phenotype are very rare. By using GTG-banding analysis, metaphase FISH, MLPA analysis, and genome-wide array CGH, we detected an unbalanced translocation involving a microdeletion of the distal part of 15q and a microduplication of the distal part of 18q. The unbalanced translocation was found in a boy that was referred with clinical suspicion of Prader-Willi syndrome.

Somatic amplifications and deletions in genome of papillary thyroid carcinomas.

Somatic gene copy number variation contributes to tumor progression. Using comparative genomic hybridization (CGH) array, the presence of genomic imbalances was evaluated in a series of 27 papillary thyroid carcinomas (PTCs). To detect only somatic imbalances, for each sample, the reference DNA was from normal thyroid tissue of the same patient.

The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines.

Since PARP-1 is supposed to be part of a multimeric repressor of sodium iodide symporter (NIS) expression, in this study the effect of the PARP inhibitor PJ34 on several properties of thyroid cancer cell lines was investigated. In TPC1, BCPAP, FRO, WRO cell lines PJ34 induced a strong increase in NIS mRNA levels. In BCPAP and TPC1 cells also significant increase of radio-iodine uptake was induced.

A new germline VHL gene mutation in three patients with apparently sporadic pheochromocytoma.

Context: Germline mutations in four genes (RET, VHL, SDHB and SDHD) are detected in about 17% of patients with apparently sporadic pheochromocytoma. Thus, genetic screening of all patients with this disease is suggested for a rational diagnostic approach and management.

Objective: To report the clinical, biochemical and genetic analysis of three unrelated patients affected by pheochromocytoma.

Sequence and copy number analyses of HEXB gene in patients affected by Sandhoff disease: functional characterization of 9 novel sequence variants.

Sandhoff disease (SD) is a lysosomal disorder caused by mutations in the HEXB gene. To date, 43 mutations of HEXB have been described, including 3 large deletions. Here, we have characterized 14 unrelated SD patients and developed a Multiplex Ligation-dependent Probe Amplification (MLPA) assay to investigate the presence of large HEXB deletions.

Cyclic AMP-response element modulator inhibits the promoter activity of the sodium iodide symporter gene in thyroid cancer cells.

Background: Comprehension of the regulatory mechanism involved in the sodium iodide symporter (NIS) expression is of great relevance for thyroid cancer. In fact, restoration of NIS expression would be a strategy to treat undifferentiated thyroid cancer. Previous in vitro findings suggest that the cyclic AMP-response element (CRE) modulator (CREM) is involved in control of NIS expression.

Expression of Dicer and Drosha in triple-negative breast cancer.

Aims: Dicer and Drosha are components of the miRNA-producing machinery and their altered expression may play a role in cancer progression. The main purpose of this study was a detailed investigation of Dicer and Drosha expression and localisation in triple-negative breast cancers.

Methods: Thirty-one triple-negative breast cancers and several breast cancer cell lines were investigated.

Histone post-translational modifications associated to BAALC expression in leukemic cells.

BAALC expression is an indicator of aggressiveness in acute myelogenous leukemia (AML). Overexpression of this gene is associated to poor of clinical outcome. It is known that post-translational histone modifications control gene transcription.

Levels of histone acetylation in thyroid tumors.

Histone acetylation is a major mechanism to regulate gene transcription. This post-translational modification is modified in cancer cells. In various tumor types the levels of acetylation at several histone residues are associated to clinical aggressiveness.

In thyroid cancer cell lines expression of periostin gene is controlled by p73 and is not related to epigenetic marks of active transcription.

Background: Periostin expression is a feature of the epithelial-mesenchymal transition, which occurs during cancer progression. Previous reports indicate that periostin expression is related to tumour aggressiveness.

Methods: In order to identify mechanisms regulating periostin expression in thyroid cancer, a panel of continuous thyroid cancer cell lines was investigated.

Nucleophosmin delocalization in thyroid tumour cells.

Nucleophosmin (NPM) is a multifunctional nucleolar protein that, depending on the context, can act as oncogene or tumour suppressor. Mutations of the NPM1 gene induce delocalization of NPM in acute myeloid leukaemia. Differently, in solid tumours, only NPM overexpression, but not delocalization, has been so far reported.

Histone deacetylase inhibitors control the transcription and alternative splicing of prohibitin in thyroid tumor cells.

Prohibitin (PHB) is a ubiquitous protein with a number of different molecular functions. PHB is involved in tumorigenesis by exerting either a permissive or blocking action on tumor growth, depending on the cell context. In the present study, we investigated the effects of the histone deacetylase inhibitors (HDACis), trichostatin A (TSA) and sodium butyrate (NaB), on PHB expression in the thyroid tumor cell lines, TPC-1 and FRO.

Quick MLPA test for quantification of SMN1 and SMN2 copy numbers.

Spinal muscular atrophy (SMA) is an autosomal recessive disease caused in about 95% of SMA patients by homozygous deletion of the survival motor neuron 1 (SMN1) gene or its conversion to the highly homologous SMN2 gene. In the majority of cases, disease severity correlates inversely with increased SMN2 copy number. Because of the comparatively high incidence of healthy carriers and severity of the disease, detection of sequence alterations and quantification of SMN1 and SMN2 copy numbers are essential for exact diagnosis and genetic counselling.