Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller’s dementia infantilis, a rare subtype of autism spectrum disorder

International audienceAbstractBackgroundDeletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD).Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling.Case presentationHere, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3.The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder.ConclusionOur present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years

Molecular and Electrophysiological Characterization of GFP-Expressing CA1 Interneurons in GAD65-GFP Mice

The use of transgenic mice in which subtypes of neurons are labeled with a fluorescent protein has greatly facilitated modern neuroscience research. GAD65-GFP mice, which have GABAergic interneurons labeled with GFP, are widely used in many research laboratories, although the properties of the labeled cells have not been studied in detail. Here we investigate these cells in the hippocampal area CA1 and show that they constitute ∼20% of interneurons in this area. The majority of them expresses either reelin (70±2%) or vasoactive intestinal peptide (VIP; 15±2%), while expression of parvalbumin and somatostatin is virtually absent. This strongly suggests they originate from the caudal, and not the medial, ganglionic eminence. GFP-labeled interneurons can be subdivided according to the (partially overlapping) expression of neuropeptide Y (42±3%), cholecystokinin (25±3%), calbindin (20±2%) or calretinin (20±2%). Most of these subtypes (with the exception of calretinin-expressing interneurons) target the dendrites of CA1 pyramidal cells. GFP-labeled interneurons mostly show delayed onset of firing around threshold, and regular firing with moderate frequency adaptation at more depolarized potentials

Sličnost ugljenohidratnog sastava otpadnog brašna heljde dokazana primenom gasne hromatografije sa masenom spektrometrijom

Gas chromatography with mass spectrometry (GC-MS) was used for performing a qualitative analysis of the hydrosoluble flour extracts of 9 buckwheat samples, taken as leftovers from restaurants. All 9 samples were first defatted with hexane. Samples of defatted flour were dried in the air and then extracted with ethanol. Ethanol extracts were used for the analysis of soluble carbohydrates. TMSi (trimethylsilylimidazole) was used as a reagent for the derivatization of carbohydrates into trimethylsilyl-ethers. The results show that the dominant trimethylsilyl-ethers of sugars are actually very similar in all buckwheat samples. The following cluster analysis was used for the comparison of the hydrosoluble extracts of 9 waste buckwheat flour samples.Kvalitativna analiza hidrosolubilnih komponenti 9 uzoraka otpadnog brašna heljde izvedena je pomoću gasne hromatografije sa masenom spektrometrijom (GC-MS). Svi uzorci prethodno su obezmašćeni heksanom. Uzorci obezmašćenog brašna osušeni su na vazduhu, nakon čega je izvršena ekstrakcija etanolom. Etanolni ekstrakti upotrebljeni su za analizu rastvorljivih ugljenih hidrata. Kao reagens za derivatizaciju ugljenih hidrata u metilsilil-etre korišćen je TMSi (trimetilsililimidazol). Rezultati pokazuju da je sastav najzastupljenijih ugljenih hidrata, odnosno njihovih trimetilsilil-etara, veoma sličan u svih 9 uzoraka heljde. U cilju poređenja hidrosolubilnog sastava etanolnih ekstrakata uzoraka otpadnog brašna heljde primenjena je klaster analiza

Sličnost lipidnog sastava otpadnog brašna heljde dokazana primenom gasne hromatografije sa masenom spektrometrijom

Gas chromatography with mass spectrometry (GC-MS) was used for performing a qualitative analysis of the liposoluble flour extracts of 9 buckwheat samples, taken as leftovers from restaurants. All 9 samples were defatted with hexane, and then those hexane extracts were used for the analysis of the fatty acids of lipid components. Transesterification reagent was TMSH (trimethylsulfonium-hydroxide, 0.2 M in methanol). With this transesterification reaction fatty acids esterified from acilglycerol to methyl-esters. The results show that the dominant methyl-esters of fatty acids are actually very similar in all buckwheat samples. The following cluster analysis was used for the comparison of the liposoluble flour extracts of 9 buckwheat waste flour samples.Za kvalitativnu analizu liposolubilnih komponenata 9 uzoraka otpadnog brašna heljde korišćena je gasna hromatografija sa masenom spektrometrijom (GC-MS). Svih 9 uzoraka prethodno je obezmašćeno heksanom, a potom su heksanski ekstrakti korišćeni za analizu sastava masnih kiselina. Reakcijom transesterifikacije masne kiseline prevedene su iz acil-glicerola u odgovarajuće metil-estre, a kao reagens za transesterifikaciju korišćen je TMSH (trimetilsulfonijum-hidroksid, 0,2 M u metanolu). Rezultati pokazuju da je sastav najzastupljenijih masnih kiselina, odnosno njihovih metil-estara, veoma sličan u svih 9 uzoraka otpadnog brašna heljde. U cilju poređenja liposolubilnog sastava heksanskih ekstrakata uzoraka otpadnog brašna heljde primenjena je klaster analiza

Developmental origin dictates interneuron AMPA and NMDA receptor subunit composition and plasticity

Disrupted excitatory synapse maturation in GABAergic interneurons may promote neuropsychiatric disorders such as schizophrenia. However, establishing developmental programs for nascent synapses in GABAergic cells is confounded by their sparsity, heterogeneity and late acquisition of subtype-defining characteristics. We investigated synaptic development in mouse interneurons targeting cells by lineage from medial ganglionic eminence (MGE) or caudal ganglionic eminence (CGE) progenitors. MGE-derived interneuron synapses were dominated by GluA2-lacking AMPA-type glutamate receptors (AMPARs), with little contribution from NMDA-type receptors (NMDARs) throughout development. In contrast, CGE-derived cell synapses had large NMDAR components and used GluA2-containing AMPARs. In neonates, both MGE- and CGE-derived interneurons expressed primarily GluN2B subunit–containing NMDARs, which most CGE-derived interneurons retained into adulthood. However, MGE-derived interneuron NMDARs underwent a GluN2B-to-GluN2A switch that could be triggered acutely with repetitive synaptic activity. Our findings establish ganglionic eminence–dependent rules for early synaptic integration programs of distinct interneuron cohorts, including parvalbumin- and cholecystokinin-expressing basket cells