New neurocutaneous syndrome with defect in cell trafficking and melanosome pathway: The future challenge

Zannolli, Raffaella; Buoni, Sabrina; Santi, M. De; Miracco, Clelia; Vonella, Giuseppina; Tassini, Maria; Vivi, Antonio; Viviano, Massimo; Rossi, Tiziana; Orsi, A; Scarinci, R; D’Ambrosio, Alfonso; Livi, Walter; Volterrani, Luca; Fois, Alberto; Willems, Patrick J.; Hayek, J.

doi:10.1016/j.braindev.2007.12.008

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…Nevertheless, no relevant studies or case reports were identified during the last decade, probably diminishing the possibility of this association), Jacobsen syndrome [Fisch et al, 2010], Joubert syndrome (Although there are a few case reports of Joubert patients with ASD [Holroyd et al, 1991; Ozonoff et al, 1999; Kumandas et al, 2004], there is more recent opposite evidence, supporting that the two disorders are distinct [Braddock et al, 2006] and their clinical similarities may be due to cerebellar abnormalities present in both conditions. Nevertheless, common variation in AHI1 , which causes Joubert syndrome type 3, was reported to contribute to ASD risk [Alvarez Retuerto et al, 2008]), Juvenile dentatorubral‐pallidoluysian atrophy [Licht and Lynch, 2002], Kabuki syndrome or Niikawa–Kuroki syndrome [Ho and Eaves, 1997; Akin Sari et al, 2008], KBG syndrome [Hah et al, 2009], Kleefstra Syndrome (http://www.ncbi.nlm.nih.gov/pubmed?term=kleefstra%20pagon), Kleine Levin syndrome [Berthier et al, 1992; Mukaddes et al, 2009], Leber's congenital amaurosis (The initial association with ASD [Rogers and Newhart‐Larson, 1989] has been diminished by recent studies reporting mild only autistic traits in a small minority of children with Leber's [Fazzi et al, 2007; den Hollander et al, 2008]), Leopard syndrome [Watanabe et al, 2010], Leukocyte adhesion deficiency type II [Gazit et al, 2010], Marineso Sjogren syndrome [Sponheim and Skjeldal, 1998], Miller–Dieker syndrome (two personal cases), MOMO syndrome [Giunco et al, 2008], Myhre syndrome [Titomanlio et al, 2001], Neuroaxonal dystrophy [Weidenheim et al, 2001], New neurocutaneous syndrome [Buoni et al, 2006; Zannolli et al, 2008], Nicolaides–Baraitser syndrome [Gana et al, 2011], Noonan syndrome [Ghazziudin et al, 1994], Ocolocutaneous albinism [Delong, 2007; Bakare and Ikegwuonu, 2008], Orstavik syndrome [Orstavik et al, 1997], PARK2 microdeletion/microduplication syndrome [Scheuerle and Wilson, 2011], Potocki–Shaffer syndrome [Swarr et al, 2010]. Rett syndrome variants (e.g., FOXG1 syndrome or Zapella variant) [Renieri et al, 2009; Kortüm et al, 2011], Rubinstein taybi syndrome [Levitas and Reid, 1998; Hellings et al, 2002; Schorry et al, 2008; Galéra et al, 2009], Septo optic dysplasia [Polizzi et al, 2006; Parr et al, 2010], Sturge–Weber syndrome (three personal cases) Trichothiodystrophy syndrome [Schepis et al, 1997], Unilateral cerebellar hypoplasia [Ramaekers et al, 1997], Unilateral ...…”

Section: Other Syndromesmentioning

confidence: 99%

Autism spectrum disorders: The quest for genetic syndromes

Zafeiriou

Ververi

Dafoulis

et al. 2013

American J of Med Genetics Pt B

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Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disabilities with various etiologies, but with a heritability estimate of more than 90%. Although the strong correlation between autism and genetic factors has been long established, the exact genetic background of ASD remains unclear. A number of genetic syndromes manifest ASD at higher than expected frequencies compared to the general population. These syndromes account for more than 10% of all ASD cases and include tuberous sclerosis, fragile X, Down, neurofibromatosis, Angelman, Prader-Willi, Williams, Duchenne, etc. Clinicians are increasingly required to recognize genetic disorders in individuals with ASD, in terms of providing proper care and prognosis to the patient, as well as genetic counseling to the family. Vice versa, it is equally essential to identify ASD in patients with genetic syndromes, in order to ensure correct management and appropriate educational placement. During investigation of genetic syndromes, a number of issues emerge: impact of intellectual disability in ASD diagnoses, identification of autistic subphenotypes and differences from idiopathic autism, validity of assessment tools designed for idiopathic autism, possible mechanisms for the association with ASD, etc. Findings from the study of genetic syndromes are incorporated into the ongoing research on autism etiology and pathogenesis; different syndromes converge upon common biological backgrounds (such as disrupted molecular pathways and brain circuitries), which probably account for their comorbidity with autism. This review paper critically examines the prevalence and characteristics of the main genetic syndromes, as well as the possible mechanisms for their association with ASD.

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Section: Other Syndromesmentioning

confidence: 99%

Autism spectrum disorders: The quest for genetic syndromes

Zafeiriou

Ververi

Dafoulis

et al. 2013

American J of Med Genetics Pt B

View full text Add to dashboard Cite

show abstract

“…The Golgi systems are also critically important for synaptic formation and function, and thus some genes can have a dual effect on neuronal phenotype [106,107]. While the importance of aberrant membrane trafficking has been seen for some time in ASD and related conditions owing to the process of synaptic vesicle formation, the critical role of the impact of these mutations on intrinsic cellular detoxification pathways has not been sufficiently recognized [108]. The finding of such mutations does not indemnify environmental stressors; Infact these individuals may be more susceptible to further detoxification damage than others.…”

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

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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New neurocutaneous syndrome with defect in cell trafficking and melanosome pathway: The future challenge

Cited by 2 publications

References 17 publications

Autism spectrum disorders: The quest for genetic syndromes

Autism spectrum disorders: The quest for genetic syndromes

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

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