Search

BackgroundVoltage-dependent anion selective channels (VDACs) are the most abundant mitochondrial outer membrane proteins, encoded in mammals by three genes,VDAC1,2and3, mostly ubiquitously expressed. As ‘mitochondrial gatekeepers’,VDACscontrol organelle and cell metabolism and are involved in many diseases. Despite the presence of numerousVDACpseudogenes in the human genome, their significance and possible role in VDAC protein expression has not yet been considered.ResultsWe investigated the relevance of processed pseudogenes of humanVDACgenes, both in physiological and in pathological contexts. Using high-throughput tools and querying many genomic and transcriptomic databases, we show that someVDACpseudogenes are transcribed in specific tissues and pathological contexts. The obtained experimental data confirm an association of theVDAC1P8pseudogene with acute myeloid leukemia (AML).ConclusionsOurin-silicocomparative analysis between theVDAC1gene and itsVDAC1P8pseudogene, together with experimental data produced in AML cellular models, indicate a specific over-expression of theVDAC1P8pseudogene in AML, correlated with a downregulation of the parentalVDAC1gene.

Background Improving the quality of information and communication is a priority in organised breast cancer screening and an ethical duty. Programmes must offer the information each woman is looking for, promoting informed decision-making. This study aimed to develop and evaluate a web-based dynamic decision aid (DA). Methods A pragmatic randomised trial carried out in six regional organised screening programmes recruited women at the first invitation receiving DA or a web-based standard brochure (SB). The primary outcome was informed choice measured on knowledge, attitudes, and intentions. Follow-up period: 7–10 days. Secondary outcomes included participation rate, satisfaction, decisional conflict, and acceptability of DA. Results Two thousand one hundred and nineteen women were randomised and 1001 completed the study. Respectively, 43.9% and 36.9% in the DA and SB reached the informed choice. The DA gave a 13-point higher proportion of women aware about overdiagnosis compared to SB (38.3% versus 25.2%, p Conclusion DA increases informed choice. Complete information including the pros, cons, controversies, and overdiagnosis–overtreatment issues boost a woman’s knowledge without reducing the rate of actual screening participation. Clinical trial registration ClinicalTrials.gov number NCT 03097653.

Typical Xq25 duplications are large and associated with heterogeneous phenotypes. Recently, small duplications involving this genomic region and encompassing the GRIA3 and STAG2 genes have been reported. These Xq25 microduplications are associated with a recognizable syndrome including intellectual disability and distinctive facial appearance. We report on Xq25 microduplications in two unrelated families identified by array comparative genomic hybridization. In both families, the genomic imbalances segregated with the disease in male individuals, while the phenotypes of the heterozygous females appeared to be modulated by their X-inactivation pattern. These rearrangements of about 600 kb involved only three genes: THOC2, XIAP, and STAG2. Further characterization by FISH analyses showed tandem duplication in the Xq25 locus of these genes. These data refine the Xq25 candidate region, identifying a minimal duplicated region of about 270 kb encompassing the XIAP and STAG2 genes. We discuss the function of the genes in the rearrangements and their involvement in the pathogenesis of this disorder.

Interstitial duplications involving chromosome 11q have rarely been reported in the literature and mainly represent large, cytogenetically detectable rearrangements associated with a wide and variable spectrum of neurodevelopmental disorders. We report on a patient affected by intellectual disability, craniosynostosis, and microcephaly. Array-CGH analysis identified a de novo 290 kb interstitial duplication of chromosome 11q13.3 including the FGF3 and FGF4 genes. Clinical comparison of our patient with those previously reported with overlapping 11q duplications allows us to define the minimal duplicated region associated with craniosynostosis and strongly supports the hypothesis that the constitutional increased dosage of the FGF3 and FGF4 genes is a risk factor for craniosynostosis in humans.

A constituição das empresas tem como intuito o lucro para remunerar os investidores. Esta pesquisa tem por objetivo analisar se existe vantagem financeira e tributária com o pagamento de juros sobre o capital próprio (JSCP) em empresas do setor agrícola. Foi realizada uma pesquisa descritiva das quatro empresas no setor de agricultura que tem capital aberto e demonstram seus relatórios publicamente no site da BM&FBOVESPA. Aplicou-se uma pesquisa documental. Verificou-se que nenhuma das empresas remunera os acionistas com distribuição de Juros sobre Capital próprio o que geraria uma economia tributária relevante. Duas empresas apresentaram prejuízo no período da pesquisa.Nelas a utilização JSCP traria benefícios somente aos acionistas.As outras duas empresas teriam economia entre 27,08% a 42,63% nos tributos incidentes sobre o lucro.

Purpose The 22q13.3 deletion syndrome, also known as Phelan–McDermid syndrome, is a rare genetic disorder characterized by hypotonia, severely impaired development of speech and language, autistic-like behaviour, and minor dysmorphic features. Neurologic problems may include seizures of different types, such as febrile, generalized tonic–clonic, focal, and absence seizures. No peculiar EEG features have been associated with 22q13 deletion syndrome to date. In order to verify if a peculiar clinical and EEG pattern is present in 22q13.3 deletion syndrome, we studied six Italian patients with this chromosome abnormality. Method Array CGH analysis was carried out in the six subjects (1 male, 5 females, age range 11–30 years, median 19.5). They underwent a complete general and neurologic examinations. The EEG study consisted of at least one awake and one nap–sleep video-EEG recordings and evaluation of other EEGs performed elsewhere. Results Three subjects suffered from myoclonic or generalized tonic–clonic seizures with a rather benign course; all showed multifocal paroxysmal abnormalities on EEG recording, predominant over the frontal–temporal regions, activated during sleep. Conclusion 22q13.3 deletion syndrome seems to be associated, at least in a subgroup of patients, with a peculiar clinical and EEG pattern, characterized by a childhood epilepsy with a rather benign evolution and with multifocal paroxysmal EEG abnormalities activated by sleep.

We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P = 5.32 x 10(-8)). Most deletion carriers showed common IGE syndromes without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia. Our results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.

Intellectual disability affects approximately 2% of the population, with affected males outnumbering affected female, partly due to disturbances involving X-linked genes. To date >90 genes associated with X-linked intellectual disability have been identified and, among these, IL1RAPL1 (interleukin 1 receptor accessory protein-like 1), was first described and mapped to Xp21.3-22.1 in 1999. Intragenic deletions of IL1RAPL1, only rarely identified, have mostly been associated with nonspecific intellectual disability (IDX) and autism spectrum disorder. Array-CGH analysis performed in our patient with intellectual disability, mild dysmorphic signs and changes in behavior identified a 285 Kb deletion in chromosome Xp21.3-21.2, with breakpoints lying in IL1RAPL1 gene intron 2 and intron 3. This is the first patient reported in literature with deletion of only exon 3 of IL1RAPL1 gene. Our patient also exhibits bilateral progressive neurosensorial deafness, which has not been previously associated with IL1RAPL1 mutations.

CGH techniques allow us to detect small duplications thatoccur in humans with phenotypic manifestations and demon-strate the importance of these duplications in the etiologyof neurodevelopmental impairment. As in the case of otherX-linked disorders, X-inactivation plays a major role in theclinical expression of such X chromosomal imbalances withusually milder symptoms in females than in males. Mostmale patients carrying Xp duplication have mental retarda-tion (X-linked mental retardation) and variable facial dys-morphic features (Gimelli

In 2003, we described (1) a broad-range denaturing gradient gel electrophoresis method for mutation scanning of the entire open reading frame and canonical splice sites of the ATRX gene (OMIM 300032), a zinc finger transcriptional regulator undergoing X inactivation and probably involved in chromatin remodeling, DNA methylation, and gene expression in mammalian development (2)(3). Mutations affecting the ATRX gene lead to the α-thalassemia/mental retardation syndrome (ATR-X syndrome; OMIM 301040). We now propose a simpler, rapid mutational approach based on denaturing HPLC (DHPLC) (4), with which we were able to confirm all of the nucleotide variations described in our first report (1) and to detect 5 other mutations in 7 of 15 unrelated Italian patients …

Correction to: European Journal of Human Genetics (2010) 18, 163–170; doi:10.1038/ejhg.2009.152; published online 7 October 2009 Since the publication of the above paper, the authors noticed that the affiliation of Umberto Balottin and Fausta Piazza is incorrect. For both the co-authors the affiliation is Child and Neuropsychiatry Unit, University of Pavia, IRCCS Fondazione C.

Correction to: European Journal of Human Genetics advance online publication 7 October 2009; doi: 10.1038/ejhg.2009.152 Since the publication of the above paper, the authors noticed a co-author was missing from the authors’ list: Dr Susan Moloney, and her affiliation is MBBS FRACP, Department of Paediatrics, Gold Coast Health Service District, Southport, Gold Coast, Queensland, Australia.