t(5;12)(p13;p13) NIPBL/ETV6

Review on t(5;12)(p13;p13) NIPBL/ETV6, with data on clinics, and the genes involved

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant

Interstitial 1q42-q44 deletion defined by fish in a short-lived female

We report a female newborn with a de novo 1q4 deletion ascertained by G bands but refined as an interstitial one by FISH with a subtelomeric 1q probe; hence, the final karyotype was 46,XX,del(1)(q42q44).ish subtellq x 2. She presented a few typical features of the del(1q42) syndrome. Additionally, she showed occipital skin aplasia, interauricular communication, and intestinal perforation-obstruction and she died at 24 days of age. This observation illustrates the clinical variability of the syndrome as well as the occasional reduced survival. The redefinition by molecular cytogenetics of a terminal deletion as an interstitial one suggests that interstitial deletions are more common than reported by classic cytogenetics and can partially account for the phenotypic variability in some deletion syndromes

Complex 9p rearrangement in an XY patient with ambiguous genitalia and features of both 9p duplication and deletion

[No abstract available

'(Dis)ordered intensification?' Techno-political models, resource access and pastoralist/agribusiness relations in the middle valley of the Senegal river

Since the 1990s, the scientific literature has shown how the technical model of intensification of livestock production is ill adapted to the characteristics of semi-arid climates and the pastoral systems operating in them. While this led to changes in the rhetoric of pastoral development, there have been no significant shifts in its conceptual foundations and working methods. This article analyses the forms of this persistence, its effects and its causes in the Valley of the Senegal River through a study of the introduction of a social business dairy project into the pastoral area surrounding the city of Richard Toll. The industrial dairy producers and the pastoralists mutually use each other for their own ends, thereby reinforcing the discrepancy between their objectives and the logic of their systems. The model of intensification is persistent because it plays a political role in constructing alliances between actors from agribusiness, and because choices about land use and resource access are depoliticised and repeatedly made in their favour. The article underlines the urgency of re-politicising and rethinking the logic behind pastoral development and the challenges it faces, and of deconstructing the rhetoric of reconciling profit with social development which serves mainly to reinforce the role that private businesses play in shaping public action

Downregulation of inducible nitric oxide synthase (iNOS) expression is implicated in the antiviral activity of acetylsalicylic acid in HCV-expressing cells

Previously, we described that acetylsalicylic acid (ASA) decreases HCV expression, but the mechanisms involved have not been clearly established. We evaluated the participation of inducible nitric oxide synthase (iNOS) in the regulation of HCV-RNA induced by ASA. Huh7 cells expressing non-structural HCV proteins were exposed to 4 mM ASA and incubated at the same times we reported HCV downregulation (24-72 h), and iNOS mRNA and protein levels were then measured by real-time PCR and Western blot, respectively. Nitric oxide levels were measured at the same time. Inhibition of iNOS mRNA by small interfering RNAs (siRNA) and activation of the iNOS gene promoter by ASA treatment were evaluated. In Huh7 replicon cells treated with ASA, we found decreased levels of iNOS mRNA, iNOS protein and nitrosylated protein levels at 48-72 h. ASA exposure also reduced the transactivation of the iNOS promoter in HCV replicon cells at 48 h, and this was partly due to the decrease in the affinity of transcription factor C/EBP-? for its binding site in the iNOS promoter. siRNA silencing of iNOS decreased HCV-RNA expression (65 %) and potentiated the antiviral effect (80 %) of ASA compared with control cells. ASA reduces iNOS expression by downregulating promoter activity, mRNA and protein levels at the same time that it decreases HCV expression. These findings suggest that the antiviral activity of ASA is mediated partially through the modulation of iNOS. Zapotitlán 2014 Springer-Verlag Wien

De novo MECP2 disomy in a Mexican male carrying a supernumerary marker chromosome and no typical Lubs syndrome features

Xq28 duplication, including the MECP2 gene, is among the most frequently identified Xq subtelomeric rearrangements. The resulting clinical phenotype is named Lubs syndrome and mainly consists of intellectual disability, congenital hypotonia, absent speech, recurrent infections, and seizures. Here we report a Mexican male patient carrying a supernumerary marker chromosome with de novo Xq28 gain. By MLPA, duplication of MECP2, GDI1, and SLC6A8 was found and a subsequent a-CGH analysis demonstrated that the gain spanned ~. 2.1. Mb. Despite gain of the MECP2 gene, the features of this patient do not evoke Lubs syndrome. Probably the mosaicism of the supernumerary marker chromosome is modifying the phenotype in this patient. � 2013 Elsevier B.V

De novo dir dup/del of 18q characterized by SNP arrays and FISH in a girl child with mixed phenotypes

[No abstract available

CDKL5 truncation due to a t(X;2)(p22.1;p25.3) in a girl with X-linked infantile spasm syndrome

[No abstract available