First case report of Cohen syndrome in the Tunisian population caused by VPS13B mutations

Rejeb, Imen; Jilani, Houweyda; Elaribi, Yasmina; Hizem, Syrine; Hila, Lamia; Zillahrdt, Julia Lauer; Chelly, Jamel; BenJemaa, Lamia

doi:10.1186/s12881-017-0493-5

Cited by 21 publications

(26 citation statements)

References 11 publications

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“…In fact, a pattern of agalactosylated and asialo‐fucosylated structures, indicative of a N‐glycan maturation defect, was found in serum proteins of these patients . Intermittent congenital neutropenia is a hallmark of this disease (detected in 168/224 VPS13B‐CDG patients) . One patient had leukopenia without neutropenia while another had pancytopenia .…”

Section: The Immunological Impact Of Glycosylation Defects—an Update mentioning

confidence: 94%

CDG and immune response: From bedside to bench and back

Pascoal

Francisco

Ferro

et al. 2019

J of Inher Metab Disea

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Glycosylation is an essential biological process that adds structural and functional diversity to cells and molecules, participating in physiological processes such as immunity. The immune response is driven and modulated by protein‐attached glycans that mediate cell‐cell interactions, pathogen recognition and cell activation. Therefore, abnormal glycosylation can be associated with deranged immune responses. Within human diseases presenting immunological defects are congenital disorders of glycosylation (CDG), a family of around 130 rare and complex genetic diseases. In this review, we have identified 23 CDG with immunological involvement, characterized by an increased propensity to—often life‐threatening—infection. Inflammatory and autoimmune complications were found in 7 CDG types. CDG natural history(ies) and the mechanisms behind the immunological anomalies are still poorly understood. However, in some cases, alterations in pathogen recognition and intracellular signaling (eg, TGF‐β1, NFAT, and NF‐κB) have been suggested. Targeted therapies to restore immune defects are only available for PGM3‐CDG and SLC35C1‐CDG. Fostering research on glycoimmunology may elucidate the involved pathophysiological mechanisms and open new therapeutic avenues, thus improving CDG patients' quality of life.

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Section: The Immunological Impact Of Glycosylation Defects—an Update mentioning

confidence: 94%

CDG and immune response: From bedside to bench and back

Pascoal

Francisco

Ferro

et al. 2019

J of Inher Metab Disea

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“…Impairment of this process at any level can lead to intracellular protein, metal, and organopollutant cellular toxicity. Mutation in genes critical for Golgi function are known in ASD, including REEP3 [88]; C3ORF58 [89]; SLC35A3 [90], neurobeachin [91]; KIRREL3 [92]; VPS13B [93] and TRAPPC6B [94]. ER genes associated with ASD risk include RELN and neuroligins [95,96].…”

Section: Phenomimicry and G X E Are Understudied But Define Environmmentioning

confidence: 99%

“…Neurobeachin [91,106,107] KIRREL3 [92] VPS13B [93] TRAPPC6B [94] ER and UPR-Inducing Genes Associated w/ASD RELN [95] Neuroligin2 [96] Neuroligin1 [97] Neuroligin3 [26] Neuroligin4 [98] GPR37 [99] GPR85 [101] RAB39B [100] NHE6 Tuberin [102] CNTNAP [104] CNTNAP2 [103] CADM1 [104,105] Flux [128] "Vaccines" not tested…”

Section: Slc35a3mentioning

confidence: 99%

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

Lw¹

2018

Autism Open Access

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Neurodevelopmental disorders, including autism spectrum disorders, have a complex biological and medical basis involving diverse genetic risk and myriad environmental exposures. Teasing apart the role of specific stressors is made challenging due to the large number of apparently contributing associations, gene x environment interactions and phenomimicry. Historically, these conditions have been rare, making causality assessment at the population level infeasible. Only a few vaccines have been tested for association with autism, and it has been shown that improved diagnosis only explains a percentage of the increase in diagnosis. Now the rates are so high in some countries that public school programs cannot handle to large numbers of special needs students, and professionals are quitting their jobs due to security concerns. Here, I present a mechanistic biomedical process model (theory) of the pathophysiology of autism that reconciles the apparent paradox between the high degree of causal heterogeneity in environmental toxins, the absence of common "autism genes" and the high degree of genetic concordance (heritability) of ASD and ASD-like traits. In brief, the environmental toxin sampling liability for ASD varies among families involving different local exposures following injury to normal cellular endoplasmic detoxification and mitochondrial processes from toxic metals. The literature strongly supports that autism is most accurately seen as an acquired cellular detoxification deficiency syndrome with heterogeneous genetic predisposition that manifests pathophysiologic consequences of accumulated, runaway cellular toxicity. At a more general level, it is a form of a toxicant-induced loss of tolerance of toxins, and of chronic and sustained ER overload ("ER hyperstress"), contributing to neuronal and glial apoptosis via the unfolded protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal re-toxification in neurons and glial cells accompanied by chronic UPR is key. This model explains the aberrant protein disorder observed in ASD; the great diversity of genes that are found to have low, but real contributions to ASD risk and the sensitivity of individuals with ASD to environmental toxins. The hindrance of detoxification and loss of cellular energetics leads to apoptosis, release of cytokines and chronic neuroinflammation and microglial activation, all observed hallmarks of ASD. Interference with the development of normal complex (redundant) synapses leads to a pathological variation in neuronal differentiation, axon and dendrite outgrowth, and synaptic protein expression. The most general outcomes are overall simplification of gross synaptic anatomy and, neurofunctionally, a loss of inhibitory feedback and aberrations in long-term connections between distant regions of the brain. Failed resolution of the ER stress response leads to redistribution of neurotoxic metals, and the impaired neurocellular processes lead to subsequent accumulation of a variety of additional types o...

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“…Hennies et al reported 17 novel VPS13B mutations among an ethnically diverse group of patients who have characteristic clinical manifestations (Hennies et al, 2004). And Rejeb et al reported a Tunisian family including two siblings with developmental delay and intellectual disability harbouring a novel compound heterozygous mutation in the VPS13B (Rejeb et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Gene analysis: A rare gene disease of intellectual deficiency‐Cohen syndrome

Yang

Hou

et al. 2018

Intl J of Devlp Neuroscience

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Cohen syndrome is a rare, genetic, connective-tissue disorder, which is caused by mutations in the gene COH1 (VPS13B, Vacuolar Protein Sorting 13 Homolog B) at the chromosome 8q22. The disease is rare reported, which major clinical features include postnatal microcephaly, obesity, short stature, intellectual disability, progressive retinal dystrophy, intermittent neutropenia and many other unusual facial feature. We report four patients in China who were diagnosed with Cohen syndrome by genetic testing and clinical manifestations. At the same time, we review the related literature, and further expound the molecular mechanism of the disease, a variety of clinical manifestations, treatment and prognosis.

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First case report of Cohen syndrome in the Tunisian population caused by VPS13B mutations

Cited by 21 publications

References 11 publications

CDG and immune response: From bedside to bench and back

CDG and immune response: From bedside to bench and back

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

Gene analysis: A rare gene disease of intellectual deficiency‐Cohen syndrome

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