scholarly journals Strong evidence for genotype–phenotype correlations in Phelan-McDermid syndrome: Results from the developmental Synaptopathies consortium

2021 ◽  
Author(s):  
Tess Levy ◽  
Jennifer H Foss-Feig ◽  
Catalina Betancur ◽  
Paige M Siper ◽  
Maria Pilar Trelles-Thorne ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Class Ii ◽  
Autism Spectrum ◽  
Class I ◽  
Sequence Variants ◽  
Ataxic Gait ◽  
Direct Evaluation ◽  
Behavioral Abnormalities ◽  
Wide Range ◽  
Phenotype Analysis

Abstract Individuals with Phelan-McDermid syndrome (PMS) present with a wide range of developmental, medical, cognitive, and behavioral abnormalities. Previous literature has begun to elucidate genotype–phenotype associations that may contribute to the wide spectrum of features. Here, we report results of genotype–phenotype associations in a cohort of 170 individuals with PMS. Genotypes were defined as Class I deletions (include SHANK3 only or SHANK3 with ARSA and/or ACR and RABL2B), Class II deletions (all other deletions), or sequence variants. Phenotype data were derived prospectively from direct evaluation, caregiver interview and questionnaires, and medical history. Analyses revealed individuals with Class I deletions or sequence variants had fewer delayed developmental milestones and higher cognitive ability compared to those with Class II deletions but had more skill regressions. Individuals with Class II deletions were more likely to have a variety of medical features, including renal abnormalities, spine abnormalities, and ataxic gait. Those with Class I deletions or sequence variants were more likely to have psychiatric diagnoses including bipolar disorder, depression, and schizophrenia. Autism spectrum disorder diagnoses did not differ between groups. This study represents the largest and most rigorous genotype–phenotype analysis in PMS to date and provides important information for considering clinical functioning, trajectories, and comorbidities as a function of specific genetic alteration.

Prevalence of Malocclusions in Autistic Patients in Isfahan

2021 ◽  
Author(s):  
Zahra Ali Mehtari ◽  
Mehdi Rafiei ◽  
Saeed Azarbayjani ◽  
Neda Ahmadi Rouzbehani ◽  
Amir Hossain Moeini
Keyword(s):  
Class Ii ◽  
Autism Spectrum ◽  
Open Bite ◽  
Class I ◽  
Dental Student ◽  
Class Iii ◽  
Cross Sectional ◽  
Deep Bite ◽  
Normal Occlusion ◽  
Age Range

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders diagnosed by impairments in social interaction and communication with repetitive and restrictive stereotyped behavioral patterns. The Prevalence of autism has been reported to be increased in recent years. This study aimed to assess the prevalence of different types of malocclusion among ASD patients in Isfahan in 2018. Materials & Methods: In a descriptive and cross-sectional trial, 92 ASD patients were studied in the age range of 7-18 years at the center for autism patients in Isfahan. Clinical oral examinations of patients are taken to assess the involved malocclusions (Cl I, Cl II and Cl III malocclusions) and malocclusion traits (deep bite, open bite and cross bite) by an educated dental student under the supervision of an orthodontist under natural light. The data are reported using frequency and percentage indices. Results: Class I malocclusion had the highest prevalence 54.3% (50) among ASD patients and the prevalence of class II and class III were found to be 19.6% (18) and 7.6% (7) respectively. The frequency of malocclusions traits of deep bite, cross bite and the open bite were 27.2% (25), 18.5% (17) and 7.6% (7) respectively. Among of the total patients, 65.2% (60) showed normal bite and 18/5% (17) showed Normal occlusion. Conclusion: ASD patients showed class I, class II and class III malocclusions from the most to least frequency and the most frequent malocclusion traits were also deep bite, cross bite and open bite respectively.

scholarly journals The duration of pubertal growth peak among three skeletal classes

2016 ◽  
Vol 21 (5) ◽  
pp. 67-74 ◽  
Author(s):  
Waqar Jeelani ◽  
◽  
Mubassar Fida ◽  
Attiya Shaikh ◽  
◽  
...  
Keyword(s):  
Class Ii ◽  
Growth Potential ◽  
Class I ◽  
Maturation Stage ◽  
Class Iii ◽  
Pubertal Growth ◽  
Lateral Cephalograms ◽  
Wide Range ◽  
Significant Difference ◽  
The Mean

ABSTRACT Introduction: Pubertal growth peak is closely associated with a rapid increase in mandibular length and offers a wide range of therapeutic modifiability. Objective: The aim of the present study was to determine and compare the mean ages of onset and duration of pubertal growth peak among three skeletal classes. Methods: A retrospective cross-sectional study was conducted using lateral cephalograms of 230 subjects with growth potential (110 males, 120 females). Subjects were categorized into three classes (Class I = 81, Class II = 82, Class III = 67), according to the sagittal relationship established between the maxilla and the mandible. The cervical vertebral maturation stage was recorded by means of Baccetti's method. The mean ages at CS3 and CS4 and the CS3-CS4 age interval were compared between boys and girls and among three skeletal classes. Results: Pubertal growth peak occurred on average four months earlier in girls than boys (p = 0.050). The average duration of pubertal growth peak was 11 months in Class I, seven months in Class II and 17 months in Class III subjects. Interclass differences were highly significant (Cohen's d > 0.08). However, no significant difference was found in the timing of pubertal growth peak onset among three skeletal classes (p = 0.126 in boys, p = 0.262 in girls). Conclusions: Girls enter pubertal growth peak on average four months earlier than boys. Moreover, the duration of pubertal growth peak is on average four months shorter in Class II and six months longer in Class III subjects as compared to Class I subjects.

scholarly journals ECOLOGICAL AND HYGIENIC ASSESSMENT OF NEW PESTICIDES FOR GRAIN CEREALS CHEMICAL PROTECTION

2021 ◽  
Vol 17 (3) ◽  
pp. 85-92
Author(s):  
M.M. Korshun ◽  
Y.V. Martіianova
Keyword(s):  
Soil Water ◽  
Field Experiments ◽  
Environmental Behavior ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Hazard Class ◽  
Soil Mesofauna ◽  
Wide Range ◽  
Mammalian Toxicity

Relevance. The use of pesticides in the national economy is to destroy or inhibit the growth of harmful plants and to protect crops from pathogens requires a mandatory assessment of their environmental hygienic hazard. Objective of our study is to assess the hazards of three new pesticides for cereal grains protection: amicarbazone from the chemical class of triazolinone compounds, bicyclopyrone from the class of tricetones and pydiflumetofen from the class of carboxamides, in terms of ecotoxicity and environmental behavior. Materials and methods. Hazard assessment of amicarbazone, bicyclopyrone and pydiflumetofen was performed on the basis of data sources on their physico-chemical characteristics, toxicometry parameters for different species of living things and indicators of environmental behavior. For potential hazards integral assess for terrestrial ecosystems an ecotox was calculated taking into account mammalian toxicity, persistence and maximum rate consumption. To identify the limiting section of migration, the mathematical modeling was performed in the systems "soil-water", "soil-plants" and "soil-atmospheric air". Results. Amicarbazone has been shown to be extremely toxic to algae and highly toxic to higher aquatic plants (HAP) (hazard class I), moderately toxic (class IV) to mammals, mildly toxic (class III) to birds, soil mesofauna and invertebrates, virtually non-toxic to bees and fish; bicyclopyrone - extremely toxic to HAP (class I) and moderately toxic (class II) to the most sensitive algae, mildly toxic (class III) to birds, fish and invertebrates and virtually non-toxic to other terrestrial fauna; pydiflumetofen is highly toxic (class I) to fish and invertebrates, moderately toxic (class II) to algae and HAP, virtually non-toxic to all terrestrial biota. Pydiflumetofen has been shown to be a highly resistant and poorly mobile in soil; amicarbazone is stable and mobile; bicyclopyrone is highly resistant in laboratory experiments and moderately stable in field experiments, its mobility varies in a wide range: from very mobile to less mobile in some soils. The danger for terrestrial biocenoses of all studied pesticides under different soil and climatic conditions is lower by (1–5) orders of magnitude in comparison with DDT; the lowest is the ecotoxicity of bicyclopyrone, the highest – pydiflumetofen. All test substances are highly stable in water. The leading section of their migration in environment is the system "soil – water of ponds" and in case of pydiflumetofen – "soil – plants" as well.

P012 An HLA Typing for every JIA?

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
N Boutrid ◽  
H Rahmoune ◽  
H Boutrid ◽  
B Bioud ◽  
M Madani ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Regulatory Region ◽  
Hla Class I ◽  
Class Ii ◽  
Hla Typing ◽  
Class I ◽  
Coding Region ◽  
Hla Dr ◽  
Hla Dq ◽  
Wide Range

Abstract Background Among the genetic susceptibility factors of Juvenile Idiopathic Arthritis (JIA), the HLA class I and II genes are the most frequently involved. These HLA genes are extensively investigated, highlighting the role of self/non-self-balance in auto-immune and auto-inflammatory diseases. Methods We carried out a retrospective study of HLA class I and/or class II genes (HLA B and HLA DR genes) of 12 children. Genotyping was performed through microlymphocytotoxicity for class I (HLA B5 and B27) and through indirect immunofluorescence and PCR for class II (HLA DR4) Results The summarized results depict:     4 patients have the HLA B27 +     3 patients have the HLA B5+     1 patient had the HLA DR JIA comprises a broad spectrum influenced by both genetic and environmental factors. The International League of Rheumatology Associations (ILAR) has defined seven categories of JIA consisting of a myriad of pediatric auto-immune and auto-inflammatory diseases. The HLA genomic region is also associated with a wide range of auto-immune diseases, encoding the HLA-DR, HLA-DQ, and HLA-DP proteins involved in the peptide’s presentations to HLA -class II-restricted CD4 + helper T cells. These mechanisms are involved in the pathogenesis of various diseases such as rheumatoid arthritis. Juvenile arthritis has also been associated with a single nucleotide polymorphism in the regulatory region of the interleukin-6 gene, close to the HLA coding region. Conclusion Genetic exploration of the HLA system in JIA, more accessible and less expensive than other targeted genetic typing, can be a helpful tool. Its usage ought to be encouraged and expanded in clinical practice.

scholarly journals The Phenotypic Spectrum of 15q13.3 Region Duplications: Report of 5 Patients

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1025
Author(s):  
Magdalena Budisteanu ◽  
Sorina Mihaela Papuc ◽  
Ioana Streata ◽  
Mihai Cucu ◽  
Andrei Pirvu ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Epileptic Seizures ◽  
Cholinergic Receptor ◽  
Molecular Data ◽  
Autism Spectrum ◽  
Chromosomal Microarray ◽  
Speech Delay ◽  
Behavioral Abnormalities ◽  
Alpha 7 ◽  
Walker Malformation

Chromosome 15q13.3 microduplications are associated with a wide spectrum of clinical presentations ranging from normal to different neuropsychiatric conditions, such as developmental delay (DD), intellectual disability (ID), epilepsy, hypotonia, autism spectrum disorders (ASD), attention-deficit hyperactivity disorder, and schizophrenia. The smallest region of overlap for 15q13.3 duplications encompasses the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, a strong candidate for the behavioral abnormalities. We report on a series of five patients with 15q13.3 duplications detected by chromosomal microarray. The size of the duplications ranged from 378 to 537 kb, and involved the CHRNA7 gene in all patients. The most common clinical features, present in all patients, were speech delay, autistic behavior, and muscle hypotonia; DD/ID was present in three patients. One patient presented epileptic seizures; EEG anomalies were observed in three patients. No consistent dysmorphic features were noted. Neuroimaging studies revealed anomalies in two patients: Dandy–Walker malformation and a right temporal cyst. 15q13.3 duplications are associated with various neuropsychiatric features, including speech delay, hypotonia, ASD, and ID, also present in our patient group. Our study brings detailed clinical and molecular data from five ASD patients with 15q13.3 microduplications involving the CHRNA7 gene, contributing to the existing knowledge about the association of 15q13.3 duplications with neuropsychiatric phenotypes.

scholarly journals Computational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders

2021 ◽  
Author(s):  
Katherine Crawford ◽  
Julie Xian ◽  
Katherine L. Helbig ◽  
Peter D. Galer ◽  
Shridhar Parthasarathy ◽  
...  
Keyword(s):  
Clinical Features ◽  
Phenotypic Variance ◽  
Loss Of Function ◽  
Phenotypic Data ◽  
Human Phenotype ◽  
Pathogenic Variants ◽  
Neonatal Onset ◽  
Behavioral Abnormalities ◽  
Wide Range ◽  
Phenotype Analysis

Abstract Purpose Pathogenic variants in SCN2A cause a wide range of neurodevelopmental phenotypes. Reports of genotype–phenotype correlations are often anecdotal, and the available phenotypic data have not been systematically analyzed. Methods We extracted phenotypic information from primary descriptions of SCN2A-related disorders in the literature between 2001 and 2019, which we coded in Human Phenotype Ontology (HPO) terms. With higher-level phenotype terms inferred by the HPO structure, we assessed the frequencies of clinical features and investigated the association of these features with variant classes and locations within the NaV1.2 protein. Results We identified 413 unrelated individuals and derived a total of 10,860 HPO terms with 562 unique terms. Protein-truncating variants were associated with autism and behavioral abnormalities. Missense variants were associated with neonatal onset, epileptic spasms, and seizures, regardless of type. Phenotypic similarity was identified in 8/62 recurrent SCN2A variants. Three independent principal components accounted for 33% of the phenotypic variance, allowing for separation of gain-of-function versus loss-of-function variants with good performance. Conclusion Our work shows that translating clinical features into a computable format using a standardized language allows for quantitative phenotype analysis, mapping the phenotypic landscape of SCN2A-related disorders in unprecedented detail and revealing genotype–phenotype correlations along a multidimensional spectrum.

Electron microscopy analysis of degenerating pancreatic ß cells in transgenic mice expressing the MHC Class I antigen Dd

1990 ◽  
Vol 48 (3) ◽  
pp. 548-549
Author(s):  
T. A. Stewart ◽  
D. Liggitt ◽  
S. Pitts ◽  
L. Martin ◽  
M. Siegel ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Disease Process ◽  
Class Ii ◽  
Class I ◽  
Type I ◽  
Aberrant Expression ◽  
Mhc Molecules ◽  
Endogenous Insulin ◽  
Class Ii Mhc ◽  
Ifn Γ

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.

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