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

Importance of Helicobacter pylori CagA and VacA natural variants upon the regulation of AGS cell cycle phase progression in vitro.

H. pylori infection is the principal cofactor for gastric cancer (GC) development. Both GC cells and colonized gastric epithelium show alterations of cell cycle progression; nonetheless, the role played by the main virulence determinants of such species, CagA and VacA, in cell turnover perturbation is not clear. Four cagA and VacA natural variants of H. pylori were examined. They were characterized for cagA, and vacA genes, CagA and VacA proteins and cytotoxicity. All strains possessed vacA. The other strain characteristics are: CCUG 17874, cagA+/CagA+/VacA+/cytotoxic; G50, cagA-/CagA-/VacA-/non-cytotoxic; G12, cagA+/CagA-/VacA+/non-cytotoxic; Ba142, cagA-/CagA-/VacA-/cytotoxic. Semiconfluent AGS cells in culture were infected in vitro with cell/organism ratios of 1:100. Uninoculated medium was the negative control. Flasks were incubated overnight; cell proliferation was evaluated by a FACS scan flow cytometer (Beckton and Dickinson, USA). Tests were performed in duplicate and results are expressed as means of the two assays. The mean percentages of cells in phase S+G2-M and infected by strains CCUG 17874, G50, G12 and Ba142, as well as uninfected cells, were respectively 24.19, 32.42, 34.63, 34.88 and 35.58 (P < 0.05, CCUG 17874 vs. the other strains and negative control). These in vitro findings suggest that only CCUG 17874 strain was able to disturb cell proliferation and that, in order to inhibit cell cycle progression in vitro, the infecting H. pylori organisms have to possess cagA, express its product, produce VacA immune reacting with an anti-VacA serum and be cytotoxic. These results may help understanding the pathogenesis of GC development