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Phelan McDermid

Cyrus Vahdatpour, Adam H Dyer, Daniela Tropea
Insulin-Like Growth Factor 1 (IGF-1) is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS) growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD), both recombinant IGF-1 (mecasermin) and related derivatives, such as (1-3)IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome...
2016: Frontiers in Neuroscience
Dongzhu Lei, Shaoyuan Li, Santasree Banerjee, Haoqing Zhang, Caiyun Li, Shuai Hou, Danjing Chen, Haiying Yan, Hanmei Li, Huan Huan Peng, Saijun Liu, Xinxin Zhang, Zhiyu Peng, Jian Wang, Huanming Yang, Hui Huang, Jing Wu
Phelan-McDermid syndrome is a neurodevelopmental disorder caused by the terminal deletion of chromosome 22 (22q13) followed by the loss of function of the SHANK3 gene. Various terminal deletions of chromosome 22q13 are associated with Phelan-McDermid with a spectrum of phenotypic severity. Here, we have done a clinical molecular study of a Chinese proband with Phelan-McDermid syndrome. Both the proband and her younger brother are associated with this syndrome while their parents are phenotypically normal. We used a karyotype in order to detect the genotype of the proband and her younger brother...
October 10, 2016: Oncotarget
Heather M Byers, Margaret P Adam, Amy LaCroix, Sarah E S Leary, Bonnie Cole, William B Dobyns, Heather C Mefford
Atypical teratoid rhabdoid tumors of the central nervous system are rare, highly malignant, embryonal tumors most often occurring in children under age 3 years. Most are due to a somatic change in tumor suppressor gene SMARCB1 followed by a second-hit, typically loss of heterozygosity, best detected on immunohistochemical staining. Despite the noteworthy genetic homogeneity of atypical teratoid rhabdoid tumors, relatively little is known about the oncogenic mechanisms that lead to biallelic inactivation of SMARCB1...
October 12, 2016: American Journal of Medical Genetics. Part A
Renée J Zwanenburg, Gianni Bocca, Selma A J Ruiter, Jan H Dillingh, Boudien C T Flapper, Edwin R van den Heuvel, Conny M A van Ravenswaaij-Arts
Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare neurodevelopmental disorder with at least 60 children and 35 adults diagnosed in the Netherlands. Clinical features are moderate to severe intellectual disability and behavioural problems in the autism spectrum. Other researchers had observed a beneficial effect of intranasal insulin on development and behaviour in a pilot study in six children with PMS. To validate this effect, we conducted a randomized, double-blind, placebo-controlled clinical trial using a stepped-wedge design...
August 31, 2016: European Journal of Human Genetics: EJHG
Chun-Xue Liu, Xiao-Lan Peng, Chun-Chun Hu, Chun-Yang Li, Qiang Li, Xiu Xu
SHANK3 is a scaffolding protein that binds to various synaptic proteins at the postsynaptic density (PSD) of excitatory glutamatergic synapses. SHANK3 is not only strongly implicated in autism spectrum disorders (ASD) but also plays a critical role in human Phelan-McDermid syndrome (22q13.3 deletion syndrome). Accumulated experimental evidence demonstrates that the zebrafish model system is useful for studying the functions of ASD-related gene during early development. However, many basic features of shank3 transcript expression in zebrafish remain poorly understood...
August 26, 2016: Development Genes and Evolution
Asher Ornoy, Liza Weinstein-Fudim, Zivanit Ergaz
Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others...
2016: Frontiers in Neuroscience
Elizabeth B Torres, Jillian Nguyen, Sejal Mistry, Caroline Whyatt, Vilelmini Kalampratsidou, Alexander Kolevzon
BACKGROUND: There is a critical need for precision phenotyping across neurodevelopmental disorders, especially in individuals who receive a clinical diagnosis of autism spectrum disorder (ASD). Phelan-McDermid deletion syndrome (PMS) is one such example, as it has a high penetrance of ASD. At present, no biometric characterization of the behavioral phenotype within PMS exists. METHODS: We introduce a data-type and statistical framework that permits the personalized profiling of naturalistic behaviors...
2016: Frontiers in Integrative Neuroscience
Tasnuva Sarowar, Resham Chhabra, Antonietta Vilella, Tobias M Boeckers, Michele Zoli, Andreas M Grabrucker
Various recent studies revealed that the proteins of the Shank family act as major scaffold organizing elements in the post-synaptic density of excitatory synapses and that their expression level is able to influence synapse formation, maturation and ultimately brain plasticity. An imbalance in Shank3 protein levels has been associated with a variety of neuropsychological and neurodegenerative disorders including autism spectrum disorders and Phelan-McDermid syndrome. Given that sleep disorders and low melatonin levels are frequently observed in autism spectrum disorders, and that circadian rhythms may be able to modulate Shank3 signaling and thereby synaptic function, here, we performed in vivo studies on CBA mice using protein biochemistry to investigate the synaptic expression levels of Shank3α during the day in different brain regions...
September 2016: Journal of Neurochemistry
Aris Giannakopoulos, Helen Fryssira, Maria Tzetis, Athina Xaidara, Christina Kanaka-Gantenbein
The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic faces. We report the occurrence of central precocious puberty in a boy diagnosed with Phelan-McDermid syndrome. At the age of 1 year, our patient presented with increased testicular volume for his age, bone age advancement and growth acceleration. Stimulated gonadotropin levels demonstrated a premature activation of the hypothalamic-pituitary-gonadal (HPG) axis...
May 28, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
Nycole A Copping, Elizabeth L Berg, Gillian M Foley, Melanie D Schaffler, Beth L Onaga, Nathalie Buscher, Jill L Silverman, Mu Yang
SHANK3 is a synaptic scaffolding protein localized in the postsynaptic density and has a crucial role in synaptogenesis and neural physiology. Deletions and point mutations in SHANK3 cause Phelan-McDermid Syndrome (PMS), and have also been implicated in autism spectrum disorder (ASD) and intellectual disabilities, leading to the hypothesis that reduced SHANK3 expression impairs basic brain functions that are important for social communication and cognition. Several mouse models of Shank3 deletions have been generated, varying in the specific domain deleted...
May 14, 2016: Neuroscience
Qiong Xu, Jennifer Goldstein, Ping Wang, Inder K Gadi, Heather Labreche, Catherine Rehder, Wei-Ping Wang, Allyn McConkie, Xiu Xu, Yong-Hui Jiang
BACKGROUND: The pathogenicity of copy number variations (CNV) in neurodevelopmental disorders is supported by research literature. However, few studies have evaluated the utility and counseling challenges of CNV analysis in clinic. METHODS: We analyzed the findings of CNV studies from a cohort referred for genetics evaluation of autism spectrum disorders (ASD), developmental disability (DD), and intellectual disability (ID). RESULTS: Twenty-two CNV in 21 out of 115 probands are considered to be pathogenic (18...
September 2016: Pediatric Research
Renée J Zwanenburg, Selma A J Ruiter, Edwin R van den Heuvel, Boudien C T Flapper, Conny M A Van Ravenswaaij-Arts
BACKGROUND: Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum. Knowledge about developmental and behavioural characteristics of this rare chromosomal disorder is still limited despite a rapid growing number of diagnoses. Our aim was to study a new and relatively large cohort to further characterize the developmental phenotype of children with PMS. METHODS: We performed a descriptive study of children with a 22q13...
2016: Journal of Neurodevelopmental Disorders
C Vicidomini, L Ponzoni, D Lim, M J Schmeisser, D Reim, N Morello, D Orellana, A Tozzi, V Durante, P Scalmani, M Mantegazza, A A Genazzani, M Giustetto, M Sala, P Calabresi, T M Boeckers, C Sala, C Verpelli
SHANK3 (also called PROSAP2) genetic haploinsufficiency is thought to be the major cause of neuropsychiatric symptoms in Phelan-McDermid syndrome (PMS). PMS is a rare genetic disorder that causes a severe form of intellectual disability (ID), expressive language delays and other autistic features. Furthermore, a significant number of SHANK3 mutations have been identified in patients with autism spectrum disorders (ASD), and SHANK3 truncating mutations are associated with moderate to profound ID. The Shank3 protein is a scaffold protein that is located in the postsynaptic density (PSD) of excitatory synapses and is crucial for synapse development and plasticity...
March 29, 2016: Molecular Psychiatry
Rosamond Rhodes, Alex Kolevzon
No abstract text is available yet for this article.
2016: American Journal of Bioethics: AJOB
A Ting Wang, Teresa Lim, Jesslyn Jamison, Lauren Bush, Latha V Soorya, Teresa Tavassoli, Paige M Siper, Joseph D Buxbaum, Alexander Kolevzon
[This corrects the article DOI: 10.1186/s11689-016-9138-9.].
2016: Journal of Neurodevelopmental Disorders
Fei Yi, Tamas Danko, Salome Calado Botelho, Christopher Patzke, ChangHui Pak, Marius Wernig, Thomas C Südhof
Heterozygous SHANK3 mutations are associated with idiopathic autism and Phelan-McDermid syndrome. SHANK3 is a ubiquitously expressed scaffolding protein that is enriched in postsynaptic excitatory synapses. Here, we used engineered conditional mutations in human neurons and found that heterozygous and homozygous SHANK3 mutations severely and specifically impaired hyperpolarization-activated cation (Ih) channels. SHANK3 mutations caused alterations in neuronal morphology and synaptic connectivity; chronic pharmacological blockage of Ih channels reproduced these phenotypes, suggesting that they may be secondary to Ih-channel impairment...
May 6, 2016: Science
A M Mieses, T Tavassoli, E Li, L Soorya, S Lurie, A T Wang, P M Siper, A Kolevzon
Phelan-McDermid syndrome (PMS), a monogenic form of autism spectrum disorder (ASD), results from deletion or mutation of the SHANK3 gene. Atypical sensory reactivity is now included in the diagnostic criteria for ASD. Examining the sensory phenotype in monogenic forms of ASD, such as PMS, may help identify underlying mechanisms of sensory reactivity. Using the Short Sensory Profile, the current study compared sensory reactivity in 24 children with PMS to 61 children with idiopathic ASD (iASD). Results suggest that children with PMS show more low energy/weak symptoms and less sensory sensitivity as compared to children with iASD...
July 2016: Journal of Autism and Developmental Disorders
A Ting Wang, Teresa Lim, Jesslyn Jamison, Lauren Bush, Latha V Soorya, Teresa Tavassoli, Paige M Siper, Joseph D Buxbaum, Alexander Kolevzon
BACKGROUND: Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder caused by deletion or mutation in the SHANK3 gene, is one of the more common single-locus causes of autism spectrum disorder (ASD). PMS is characterized by global developmental delay, hypotonia, delayed or absent speech, increased risk of seizures, and minor dysmorphic features. Impairments in language and communication are one of the most consistent characteristics of PMS. Although there is considerable overlap in the social communicative deficits associated with PMS and ASD, there is a dearth of data on underlying abnormalities at the level of neural systems in PMS...
2016: Journal of Neurodevelopmental Disorders
Michael Bidinosti, Paolo Botta, Sebastian Krüttner, Catia C Proenca, Natacha Stoehr, Mario Bernhard, Isabelle Fruh, Matthias Mueller, Debora Bonenfant, Hans Voshol, Walter Carbone, Sarah J Neal, Stephanie M McTighe, Guglielmo Roma, Ricardo E Dolmetsch, Jeffrey A Porter, Pico Caroni, Tewis Bouwmeester, Andreas Lüthi, Ivan Galimberti
SH3 and multiple ankyrin repeat domains 3 (SHANK3) haploinsufficiency is causative for the neurological features of Phelan-McDermid syndrome (PMDS), including a high risk of autism spectrum disorder (ASD). We used unbiased, quantitative proteomics to identify changes in the phosphoproteome of Shank3-deficient neurons. Down-regulation of protein kinase B (PKB/Akt)-mammalian target of rapamycin complex 1 (mTORC1) signaling resulted from enhanced phosphorylation and activation of serine/threonine protein phosphatase 2A (PP2A) regulatory subunit, B56β, due to increased steady-state levels of its kinase, Cdc2-like kinase 2 (CLK2)...
March 11, 2016: Science
J I M Egger, R J Zwanenburg, C M A van Ravenswaaij-Arts, T Kleefstra, W M A Verhoeven
Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by a variable degree of intellectual disability, impaired speech and language as well as social communicative skills and mild dysmorphic features. The SHANK3 gene is thought to be a major contributor to the phenotype. Apart from the syndrome-associated autistic features, symptoms from the bipolar spectrum can be discerned, in particular behavior instability and fluctuating mood culminating in a (hypo)manic state. In case of coincident major somatic events, a deteriorating course may occur...
April 2016: Genes, Brain, and Behavior
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