Zinc deficiency and supplementation in autism spectrum disorder and<scp>Phelan‐McDermid</scp>syndrome

Alsufiani, Hadeil M.; Alkhanbashi, Alaa S; Laswad, Norah A Bin; Bakhadher, Khulood K; AlGhamdi, Shareefa A.; Tayeb, Haythum O.; Tarazi, Frank I.

doi:10.1002/jnr.25019

Cited by 13 publications

(12 citation statements)

References 75 publications

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“…Zinc is a metal involved in the developmental and functioning of the central nervous system (CNS) and is crucial for normal cognitive functions and emotional behaviors. Zn is also responsible for maintaining viable synapses by stabilizing SHANK2/3 postsynaptic scaffolding proteins [33,34]. Zn deficiency is a risk factor that may contribute to the pathophysiology of neurodevelopmental disorders such as ASD.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel SHANK2 Pathogenic Variant in a Patient with a Neurodevelopmental Disorder

Doddato

Fabbiani

Scandurra

et al. 2022

Genes

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Genetic defects in the SHANK2 gene, encoding for synaptic scaffolding protein, are associated with a variety of neurodevelopmental conditions, including autism spectrum disorders and mild to moderate intellectual disability. Until now, limited patient clinical descriptions have been published. Only 13 unrelated patients with SHANK2 pathogenic variations or microdeletions have been reported worldwide. By Exome Sequencing, we identified a de novo stop-gain variant, c.334C>T, p.(Gln112*), in an Italian patient with a neurodevelopmental disorder. The patient (9 years old) presented the following facial features: a flat profile, thick eyebrows, long eyelashes, a bulbous nasal tip and a prominent columella, retracted ears, dental anomalies. The patient showed speech delay and mild neuromotor delay but not autism spectrum disorder. In conclusion, this patient with a novel pathogenic variant in SHANK2 enlarges the phenotypic spectrum of SHANK2-mutated patients and demonstrates that the severity of SHANK2-associated disorders is highly variable.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel SHANK2 Pathogenic Variant in a Patient with a Neurodevelopmental Disorder

Doddato

Fabbiani

Scandurra

et al. 2022

Genes

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“…Other neuropsychiatric manifestations include epilepsy, bipolar disorder, and schizophrenia. 3,18 The classification of PMS is made according to the involvement of the SHANK3 gene.…”

Section: Experiences Surrounding the Diagnostic Process And Care Amon...mentioning

confidence: 99%

“…Due to the variability of the PMS phenotype, shankopathies may present with neurodevelopmental impairment, neonatal hypotonia, intellectual disability, and/or ASD‐like symptoms. Other neuropsychiatric manifestations include epilepsy, bipolar disorder, and schizophrenia 3,18 . The classification of PMS is made according to the involvement of the SHANK3 gene.…”

mentioning

confidence: 99%

Experiences surrounding the diagnostic process and care among parents of children diagnosed with Phelan–McDermid syndrome: A qualitative study

García‐Bravo

Martínez-Piédrola

García‐Bravo

et al. 2022

Develop Med Child Neuro

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To explore the experience of parents of children diagnosed with Phelan-McDermid syndrome (PMS) with regard to the diagnostic process, treatment, and medical care. Method: A qualitative descriptive study was conducted. Participants were recruited using non-probabilistic purposeful sampling. In total, 32 parents with children with PMS were included. In-depth interviews and researcher field notes were used. An inductive thematic analysis was performed. Results: Five themes were identified: (1) the 'diagnostic process' describes the diagnostic process and how it is communicated to the parents; (2) 'treatment and expectations' describes the expectations and hopes placed on future treatment; (3) 'family planning' describes how parents deal with genetic counselling when planning to have more children after a diagnosis of PMS; (4) 'the world of disability' describes the entry of parents into an environment of dependency and disability after the diagnosis; (5) 'family's financial situation' highlights the financial difficulties due to the high cost of therapies and daily care products. Interpretation: Our results provide insight on how a diagnosis of PMS and its consequences are experienced by parents of children with PMS. These results can be used by health professionals to help and support parents.

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“…A key ASD therapeutic agent that has shown its effectiveness in treating ASDs through NMDAR modulation is zinc [ 344 , 345 , 346 , 347 ]. The hypothesis of zinc supplementation as a potent treatment strategy for ASDs has stemmed from reports that reduced serum zinc levels have been identified in autistic individuals (discussed further in Section 4 ) [ 348 , 349 , 350 , 351 , 352 ].…”

Section: Effects Of Zinc On Nmdars In Asdsmentioning

confidence: 99%

The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders

et al. 2022

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NMDA-type glutamate receptors are critical for synaptic plasticity in the central nervous system. Their unique properties and age-dependent arrangement of subunit types underpin their role as a coincidence detector of pre- and postsynaptic activity during brain development and maturation. NMDAR function is highly modulated by zinc, which is co-released with glutamate and concentrates in postsynaptic spines. Both NMDARs and zinc have been strongly linked to autism spectrum disorders (ASDs), suggesting that NMDARs are an important player in the beneficial effects observed with zinc in both animal models and children with ASDs. Significant evidence is emerging that these beneficial effects occur via zinc-dependent regulation of SHANK proteins, which form the backbone of the postsynaptic density. For example, dietary zinc supplementation enhances SHANK2 or SHANK3 synaptic recruitment and rescues NMDAR deficits and hypofunction in Shank3ex13–16−/− and Tbr1+/− ASD mice. Across multiple studies, synaptic changes occur in parallel with a reversal of ASD-associated behaviours, highlighting the zinc-dependent regulation of NMDARs and glutamatergic synapses as therapeutic targets for severe forms of ASDs, either pre- or postnatally. The data from rodent models set a strong foundation for future translational studies in human cells and people affected by ASDs.

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Zinc deficiency and supplementation in autism spectrum disorder andPhelan‐McDermidsyndrome

Cited by 13 publications

References 75 publications

Identification of a Novel SHANK2 Pathogenic Variant in a Patient with a Neurodevelopmental Disorder

Identification of a Novel SHANK2 Pathogenic Variant in a Patient with a Neurodevelopmental Disorder

Experiences surrounding the diagnostic process and care among parents of children diagnosed with Phelan–McDermid syndrome: A qualitative study

The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders

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