Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.284
Filtrar
1.
Transl Psychiatry ; 12(1): 210, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597773

RESUMO

Imprinted genes are a subset of mammalian genes that are subject to germline parent-specific epigenetic modifications leading monoallelic expression. Imprinted gene expression is particularly prevalent in the brain and it is unsurprising that mutations affecting their expression can lead to neurodevelopmental and/or neuropsychiatric disorders in humans. Here I review the evidence for this, detailing key neurodevelopmental disorders linked to imprinted gene clusters on human chromosomes 15q11-q13 and 14q32, highlighting genes and possible regulatory links between these different syndromes. Similarly, rare copy number variant mutations at imprinted clusters also provide strong links between abnormal imprinted gene expression and the predisposition to severe psychiatric illness. In addition to direct links between brain-expressed imprinted genes and neurodevelopmental and/or neuropsychiatric disorders, I outline how imprinted genes that are expressed in another tissue hotspot, the placenta, contribute indirectly to abnormal brain and behaviour. Specifically, altered nutrient provisioning or endocrine signalling by the placenta caused by abnormal expression of imprinted genes may lead to increased prevalence of neurodevelopmental and/or neuropsychiatric problems in both the offspring and the mother.


Assuntos
Impressão Genômica , Transtornos do Neurodesenvolvimento , Animais , Encéfalo/metabolismo , Variações do Número de Cópias de DNA , Epigênese Genética , Humanos , Mamíferos , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/metabolismo
2.
J Neurodev Disord ; 14(1): 27, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501684

RESUMO

BACKGROUND: The development of advanced genetic technologies has resulted in rapid identification of genetic etiologies of neurodevelopmental disorders (NDDs) and has transformed the classification and diagnosis of various NDDs. However, diagnostic genetics has far outpaced our ability to provide timely medical counseling, guidance, and care for patients with genetically defined NDDs. These patients and their caregivers present with an unmet need for care coordination across multiple domains including medical, developmental, and psychiatric care and for educational resources and guidance from care professionals. After a genetic diagnosis is made, families also face several barriers in access to informed diagnostic evaluations and medical support. METHODS: As part of Care and Research in Neurogenetics (CARING), a multidisciplinary clinical program for children and adults with neurogenetic disorders, we conducted qualitative clinical interviews about the diagnostic journey of families. This included the overall timeline to receiving diagnoses, experiences before and after diagnosis, barriers to care, and resources that helped them to navigate the diagnostic process. RESULTS: A total of 37 interviews were conducted with parents of children ages 16 months to 33 years. Several key themes were identified: (1) delays between initial caregiver observations and formal developmental or genetic diagnoses; (2) practical barriers to clinical evaluation and care, including long wait times for an appointment, lack of insurance coverage, availability of local evaluations, transportation difficulties, and native language differences; (3) the importance of being part of a patient advocacy group to help navigate the diagnostic journey; and (4) unique challenges faced by adults (18 years or older). CONCLUSIONS: Families of children with complex neurodevelopmental and genetic disabilities face numerous challenges in finding adequate medical care and services for their child. They experience considerable delays in receiving timely diagnoses and face significant barriers that further delay the process of receiving access to services needed for the child's continued care. The gaps indicated in this study speak to the need for more comprehensive coordination of care for patients with intellectual and developmental disabilities, as well as the development of systematic, disorder-specific resources both for providers and families in order to improve patient outcomes.


Assuntos
Transtornos do Neurodesenvolvimento , Adulto , Cuidadores/psicologia , Criança , Família , Humanos , Lactente , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Pais/psicologia
3.
Eur J Med Genet ; 65(6): 104520, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35568357

RESUMO

Microcephaly is a frequent feature of neurodevelopmental disorders (NDDs). Our study presents the heterogeneous spectrum of genetic disorders in patients with microcephaly either in isolated form or in association with other neurological and extra-neural abnormalities. We present data of 91 patients from 87 unrelated families referred to our clinic during 2016-2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations in autosomal recessive genes were identified 31 were homozygotes (including 16 from non-consanguineous families). The study added 28 novel pathogenic/likely pathogenic variations. The study also calls attention to phenotypic variability and expansion in spectrum as well as uncovers genes where microcephaly is not reported previously or is a rare finding. We here report phenotypes associated with the genes for ultra-rare NDDs with microcephaly namely ATRIP, MINPP1, PNPLA8, AIMP2, ANKLE2, NCAPD2 and TRIT1.


Assuntos
Microcefalia , Transtornos do Neurodesenvolvimento , Proteínas Cromossômicas não Histona/genética , Exoma , Genes Recessivos , Humanos , Transtornos do Neurodesenvolvimento/genética , Proteínas Nucleares/genética , Linhagem , Proteínas de Ligação a Poli-ADP-Ribose/genética , Sequenciamento Completo do Exoma
4.
Front Endocrinol (Lausanne) ; 13: 860110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370942

RESUMO

The internal and external environment of the mother during the developmental stages of the fetus affects the offspring's health. According to the developmental origins of health and disease (DOHaD) theory, environmental factors influence the offspring and also affect health in adulthood. Recently, studies based on this theory have gained attracted attention because of their clinical utility in identifying the risk groups for various diseases. Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) can be caused by exposure to certain prenatal environments during pregnancy. This review describes the latest findings on the effect of prenatal environment on the onset mechanism of NDDs based on the DOHaD theory. Unravelling the molecular mechanisms underlying the pathogenesis of NDDs is important, because there are no therapeutic drugs for these disorders. Furthermore, elucidating the relationship between the DOHaD theory and NDDs will contribute to the popularization of preventive medicine.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Espectro Autista/complicações , Feminino , Humanos , Mães , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Fatores de Risco
5.
Int J Mol Sci ; 23(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35409306

RESUMO

Rare diseases are those which affect a small number of people compared to the general population. However, many patients with a rare disease remain undiagnosed, and a large majority of rare diseases still have no form of viable treatment. Approximately 40% of rare diseases include neurologic and neurodevelopmental disorders. In order to understand the characteristics of rare neurological disorders and identify causative genes, various model organisms have been utilized extensively. In this review, the characteristics of model organisms, such as roundworms, fruit flies, and zebrafish, are examined, with an emphasis on zebrafish disease modeling in rare neurological disorders.


Assuntos
Doenças do Sistema Nervoso , Transtornos do Neurodesenvolvimento , Animais , Modelos Animais de Doenças , Humanos , Doenças do Sistema Nervoso/genética , Doenças Raras , Peixe-Zebra/genética
6.
Genome Med ; 14(1): 40, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35468861

RESUMO

BACKGROUND: Previous large-scale studies of de novo variants identified a number of genes associated with neurodevelopmental disorders (NDDs); however, it was also predicted that many NDD-associated genes await discovery. Such genes can be discovered by integrating copy number variants (CNVs), which have not been fully considered in previous studies, and increasing the sample size. METHODS: We first constructed a model estimating the rates of de novo CNVs per gene from several factors such as gene length and number of exons. Second, we compiled a comprehensive list of de novo single-nucleotide variants (SNVs) in 41,165 individuals and de novo CNVs in 3675 individuals with NDDs by aggregating our own and publicly available datasets, including denovo-db and the Deciphering Developmental Disorders study data. Third, summing up the de novo CNV rates that we estimated and SNV rates previously established, gene-based enrichment of de novo deleterious SNVs and CNVs were assessed in the 41,165 cases. Significantly enriched genes were further prioritized according to their similarity to known NDD genes using a deep learning model that considers functional characteristics (e.g., gene ontology and expression patterns). RESULTS: We identified a total of 380 genes achieving statistical significance (5% false discovery rate), including 31 genes affected by de novo CNVs. Of the 380 genes, 52 have not previously been reported as NDD genes, and the data of de novo CNVs contributed to the significance of three genes (GLTSCR1, MARK2, and UBR3). Among the 52 genes, we reasonably excluded 18 genes [a number almost identical to the theoretically expected false positives (i.e., 380 × 0.05 = 19)] given their constraints against deleterious variants and extracted 34 "plausible" candidate genes. Their validity as NDD genes was consistently supported by their similarity in function and gene expression patterns to known NDD genes. Quantifying the overall similarity using deep learning, we identified 11 high-confidence (> 90% true-positive probabilities) candidate genes: HDAC2, SUPT16H, HECTD4, CHD5, XPO1, GSK3B, NLGN2, ADGRB1, CTR9, BRD3, and MARK2. CONCLUSIONS: We identified dozens of new candidates for NDD genes. Both the methods and the resources developed here will contribute to the further identification of novel NDD-associated genes.


Assuntos
Variações do Número de Cópias de DNA , Transtornos do Neurodesenvolvimento , Proteínas de Ciclo Celular/genética , DNA Helicases/genética , Éxons , Humanos , Proteínas do Tecido Nervoso/genética , Transtornos do Neurodesenvolvimento/genética , Nucleotídeos , Fatores de Transcrição/genética
7.
Rev Neurol ; 74(9): 291-297, 2022 05 01.
Artigo em Espanhol | MEDLINE | ID: mdl-35484700

RESUMO

INTRODUCTION: Digital screen time has been largely studied in children populations, but few have focused on children with neurodevelopmental disorders. Our main objective was to study the characteristics of use of recreational screens (television (TV) and video games), in children with neurodevelopmental disorders. SUBJECTS AND METHODS: We conducted a case-control study in which children with neurodevelopmental disorders under the age of 6 were compared with controls of the same age range. We analysed TV and video game exposure through a designed questionnaire for parents that included daily time exposure, sociodemographic characteristics, home media environment, sociocultural habits, attitudes and beliefs about TV. RESULTS: Sixty-one individuals with developmental and 153 controls were enrolled. Children with developmental problems spend more time watching TV than controls (124,4 ± 83,4 vs 71,5 ± 47,4 min / day p <0,001), while video game time was similar in both groups (37,6 ± 39, 6 vs 31,7 ± 32,6 min / day p = 0,138). Children with neurodevelopmental disorders began earlier to watch TV than controls. There were no relevant differences between groups in demographics, Sociocultural, environmental and attitudinal and belief variables. CONCLUSIONS: Children with neurodevelopmental disorders start watching TV at an earlier age and consume more screen time than healthy children. Our findings indicate that Children with neurodevelopmental disorders are more vulnerable to screen abuse, and stress the importance to offer anticipatory guidance to their parents.


TITLE: Estudio comparativo del tiempo de pantallas recreativas en los trastornos del neurodesarrollo.Introducción. En poblaciones infantiles, el tiempo de consumo de pantallas recreativas se ha estudiado ampliamente, pero se dispone de menos información en niños con trastornos del neurodesarrollo. Nuestro principal objetivo era estudiar las características de uso de las pantallas recreativas (televisión y videojuegos) en niños con trastornos del neurodesarrollo. Sujetos y métodos. Realizamos un estudio de casos y controles, comparando niños con y sin trastornos del neurodesarrollo menores de 6 años. A través de un cuestionario rellenado por los progenitores, se analizó el tiempo de exposición diaria a pantallas recreativas, las características sociodemográficas y ambientales, los hábitos socioculturales y las actitudes relacionadas con las pantallas recreativas. Resultados. Se analizó a 61 individuos con trastorno del neurodesarrollo y a 153 controles. Los casos pasaron más tiempo mirando la televisión (124,4 ± 83,4 frente a 71,5 ± 47,4 minutos/día; p menor de 0,001), mientras que el tiempo de videojuegos fue similar en ambos grupos (37,6 ± 39, 6 frente a 31,7 ± 32,6 minutos/día; p = 0,138). Los niños con trastorno del neurodesarrollo empezaron a una edad más temprana a ver televisión. No hubo diferencias relevantes entre los dos grupos en características sociodemográficas, socioculturales, ambientales y de actitud relacionadas con las pantallas recreativas. Conclusiones. Los niños con trastorno del neurodesarrollo empiezan a ver la televisión a una edad más temprana y consumen más tiempo que sus coetáneos sanos. Nuestros hallazgos indican que los niños con trastornos del neurodesarrollo son más vulnerables al abuso de la televisión, por lo que consideramos relevante ofrecer una guía anticipada a sus progenitores.


Assuntos
Transtornos do Neurodesenvolvimento , Jogos de Vídeo , Estudos de Casos e Controles , Criança , Humanos , Tempo de Tela , Televisão
8.
Eur J Med Genet ; 65(6): 104515, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35487419

RESUMO

Intellectual disability is characterized by a significant impaired intellectual and adaptive functioning, affecting approximately 1-3% of the population, which can be caused by a variety of environmental and genetic factors. In this respect, de novo heterozygous HECW2 variants were associated recently with neurodevelopmental disorders associated to hypotonia, seizures, and absent language. HECW2 encodes an E3 ubiquitin-protein ligase that stabilizes and enhances transcriptional activity of p73, a key factor regulating proliferation, apoptosis, and neuronal differentiation, which are together essential for proper brain development. Here, using whole exome sequencing, we identified a homozygous nonsense HECW2 variant: c.736C > T; p.Arg246* in a proband from a Moroccan consanguineous family, with developmental delay, intellectual disability, hypotonia, generalized tonico-clonic seizures and a persistent tilted head. Thus this study describes the first homozygous HECW2 variant, inherited as an autosomal recessive pattern, contrasting with former reported de novo variants found in HECW2 patients.


Assuntos
Deficiência Intelectual , Malformações do Sistema Nervoso , Transtornos do Neurodesenvolvimento , Homozigoto , Humanos , Deficiência Intelectual/genética , Hipotonia Muscular/genética , Transtornos do Neurodesenvolvimento/genética , Convulsões/genética , Ubiquitina-Proteína Ligases/genética
9.
Genes (Basel) ; 13(4)2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-35456494

RESUMO

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.


Assuntos
Transtorno do Espectro Autista , Deficiência Intelectual , Transtornos do Desenvolvimento da Linguagem , Transtornos do Neurodesenvolvimento , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Criança , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Proteínas do Tecido Nervoso/genética , Transtornos do Neurodesenvolvimento/genética , Sequenciamento Completo do Exoma
10.
Am J Hum Genet ; 109(4): 601-617, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35395208

RESUMO

Neurodevelopmental disorders are highly heterogenous conditions resulting from abnormalities of brain architecture and/or function. FBXW7 (F-box and WD-repeat-domain-containing 7), a recognized developmental regulator and tumor suppressor, has been shown to regulate cell-cycle progression and cell growth and survival by targeting substrates including CYCLIN E1/2 and NOTCH for degradation via the ubiquitin proteasome system. We used a genotype-first approach and global data-sharing platforms to identify 35 individuals harboring de novo and inherited FBXW7 germline monoallelic chromosomal deletions and nonsense, frameshift, splice-site, and missense variants associated with a neurodevelopmental syndrome. The FBXW7 neurodevelopmental syndrome is distinguished by global developmental delay, borderline to severe intellectual disability, hypotonia, and gastrointestinal issues. Brain imaging detailed variable underlying structural abnormalities affecting the cerebellum, corpus collosum, and white matter. A crystal-structure model of FBXW7 predicted that missense variants were clustered at the substrate-binding surface of the WD40 domain and that these might reduce FBXW7 substrate binding affinity. Expression of recombinant FBXW7 missense variants in cultured cells demonstrated impaired CYCLIN E1 and CYCLIN E2 turnover. Pan-neuronal knockdown of the Drosophila ortholog, archipelago, impaired learning and neuronal function. Collectively, the data presented herein provide compelling evidence of an F-Box protein-related, phenotypically variable neurodevelopmental disorder associated with monoallelic variants in FBXW7.


Assuntos
Proteína 7 com Repetições F-Box-WD , Transtornos do Neurodesenvolvimento , Ubiquitinação , Proteína 7 com Repetições F-Box-WD/química , Proteína 7 com Repetições F-Box-WD/genética , Proteína 7 com Repetições F-Box-WD/metabolismo , Células Germinativas , Mutação em Linhagem Germinativa , Humanos , Transtornos do Neurodesenvolvimento/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
11.
Nature ; 604(7906): 509-516, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35396579

RESUMO

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10-6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.


Assuntos
Mutação , Transtornos do Neurodesenvolvimento , Esquizofrenia , Estudos de Casos e Controles , Exoma , Predisposição Genética para Doença/genética , Humanos , Transtornos do Neurodesenvolvimento/genética , Receptores de N-Metil-D-Aspartato/genética , Esquizofrenia/genética
12.
Int J Mol Sci ; 23(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35457207

RESUMO

The postsynaptic density (PSD) is a massive protein complex, critical for synaptic strength and plasticity in excitatory neurons. Here, the scaffolding protein PSD-95 plays a crucial role as it organizes key PSD components essential for synaptic signaling, development, and survival. Recently, variants in DLG4 encoding PSD-95 were found to cause a neurodevelopmental disorder with a variety of clinical features including intellectual disability, developmental delay, and epilepsy. Genetic variants in several of the interaction partners of PSD-95 are associated with similar phenotypes, suggesting that deficient PSD-95 may affect the interaction partners, explaining the overlapping symptoms. Here, we review the transmembrane interaction partners of PSD-95 and their association with neurodevelopmental disorders. We assess how the structural changes induced by DLG4 missense variants may disrupt or alter such protein-protein interactions, and we argue that the pathological effect of DLG4 variants is, at least partly, exerted indirectly through interaction partners of PSD-95. This review presents a direction for functional studies to elucidate the pathogenic mechanism of deficient PSD-95, providing clues for therapeutic strategies.


Assuntos
Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Proteína 4 Homóloga a Disks-Large/genética , Proteína 4 Homóloga a Disks-Large/metabolismo , Humanos , Deficiência Intelectual/metabolismo , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/metabolismo , Fenótipo , Densidade Pós-Sináptica/metabolismo , Sinapses/metabolismo
13.
Life Sci ; 298: 120526, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35367466

RESUMO

Lactation is a crucial postnatal programming window which can interfere with child development and predispose to metabolic disorders later in life, as insulin resistance and obesity. Although breastfeeding is known to prevent many diseases in the newborn, changes in milk composition have been correlated with alterations in central nervous system maturation and differentiation. Changes in milk quality and quantity may predispose to metabolic disorders later in life but have also been linked to the development of neuronal diseases. Maternal metabolic condition, diet and behaviours have been considered determinant for metabolic programming in the child, although the mechanisms involved remain to be elucidated. Some of such mechanisms may also be related with the increasing prevalence of neurodevelopmental and behavioural diseases in the younger generations. This review focuses on the interconnected risks between changes of maternal metabolic status/unbalanced diets during lactation and offspring's development of metabolic and neurodevelopmental disorders. Furthermore, the present review reunites the current knowledge about the mechanisms underlying the association between these disorders and highlights the need of further exploring the impact of lactation period on neurodevelopmental and metabolic outcomes.


Assuntos
Doenças Metabólicas , Transtornos do Neurodesenvolvimento , Aleitamento Materno , Criança , Feminino , Humanos , Recém-Nascido , Lactação/fisiologia , Fenômenos Fisiológicos da Nutrição Materna , Transtornos do Neurodesenvolvimento/etiologia , Responsabilidade Social
14.
BMC Health Serv Res ; 22(1): 472, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35399084

RESUMO

INTRODUCTION: The current COVID-19 pandemic interferes with family lives across the world, particularly families of children with neurodevelopmental disorders (NDDs) are at a greater risk for being negatively impacted by the pandemic. Together with representatives from this caregiver population the aim was to explore the interference associated with normal family life caused by the COVID-19 pandemic. METHOD: This is a descriptive study using a cross-sectional design. Following a strategic network sampling strategy, a user-developed national survey was completed by a larger sample (N = 1,186) of parents and informal caregivers of children with NDDs. The survey utilized a combination of both closed and open-ended questions, and a logistic regression analysis was carried out to assess the association between family characteristics, characteristics of the child, and COVID-19 related family life interference. Before carrying out the regression an inductive content analysis of the open-ended question on `How has the isolation affected the family´ was carried out to construct the outcome variable. RESULTS: The initial analysis indicated that the COVID-19 pandemic induced a shift in everyday family life and a lack of guidance and support related to managing the challenges they were facing. Caregivers who reported that COVID-19 had significantly interfered with their family life, were more likely to report having anxious children, and to have experienced an increased number of conflicts at home. The logistic regression showed that both anxious children and increased conflicts considerably increased the risk for reporting family life interference compared to those that reported no increased conflicts or anxious children. DISCUSSION: Considering how the COVID-19 related increased conflicts at home and anxious children threaten the family life of the NDD caregiver population, as an external source of family stress, which might lead to negative impact on their mental and physical well-being, the need for further research in collaboration with user representatives is apparent. Our study suggests that more information should be provided to healthcare providers, social professionals, peers, people with NDDs, and caregivers of people with NDDs about the potential threats that a stressful life event such as the current pandemic can pose to their mental and physical health and their family life.


Assuntos
COVID-19 , Transtornos do Neurodesenvolvimento , COVID-19/epidemiologia , Cuidadores , Criança , Estudos Transversais , Humanos , Transtornos do Neurodesenvolvimento/epidemiologia , Pandemias
15.
Clin Psychol Rev ; 94: 102155, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35397441

RESUMO

Interpretation and response to behaviour is predicated on understanding. However, our present understanding of aggressive behaviour, especially for complex and vulnerable populations is limited. The purpose of this review is to enhance our understanding of aggressive behaviour by providing a comprehensive outline of the conditions and underlying mechanisms that drive aggressive behaviour for children and adolescents with neurodevelopmental disorders (NDDs), focusing on Fetal Alcohol Spectrum Disorder (FASD). This review will: (1) Synthesize the present literature regarding aggressive behaviour, via the cognitive, environmental, and emotional factors that drive it, for children and adolescents with NDDs; (2) Identify and integrate information specific to the elevated vulnerability for aggressive behaviour that FASD poses; and (3) Utilize the information derived from the review to propose frameworks, in the form of two corresponding models, for recognizing and responding to aggressive behaviour. The advantages of such neurodevelopmentally guided, comprehensive, and integrative framework are to clarify predisposing and perpetuating mechanisms, inform appropriate caregiver and caseworker support, and inform clinicians' preliminary intervention. These ultimately should improve the ability to respond and promote healthy outcomes for these vulnerable youngsters.


Assuntos
Transtornos do Espectro Alcoólico Fetal , Transtornos do Neurodesenvolvimento , Adolescente , Agressão , Cuidadores , Criança , Feminino , Humanos , Gravidez , Violência
16.
Eur J Med Genet ; 65(6): 104481, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35398349

RESUMO

Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB; MIM# 619121) is a recently described metabolic disorder with characteristic features of mild dysmorphism, intellectual disability, spasticity, peripheral neuropathy, cardiomyopathy, and thin corpus callosum. Biallelic variants in SHMT2 (MIM 138450), encoding mitochondrial serine hydroxymethyltransferase enzyme, have been recently linked to this disorder. Till now, a total of seven variants including six missense and one deletion-insertion has been reported in SHMT2. We hereby report an additional individual with novel homozygous missense variant c.1133A > G in SHMT2 (NM_005412.6) identified by exome sequencing and review the phenotype and genotype of the previously reported individuals with NEDCASB.


Assuntos
Encefalopatias , Cardiomiopatias , Deficiência Intelectual , Malformações do Sistema Nervoso , Transtornos do Neurodesenvolvimento , Encéfalo/diagnóstico por imagem , Cardiomiopatias/genética , Humanos , Deficiência Intelectual/genética , Espasticidade Muscular/genética , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Sequenciamento Completo do Exoma
17.
Dis Model Mech ; 15(5)2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363276

RESUMO

Recent studies have indicated that some phenotypes caused by decreased function of select neurodevelopmental disorder (NDD) risk genes can be reversed by restoring gene function in adulthood. However, few of the hundreds of risk genes have been assessed for adult phenotypic reversibility. We developed a strategy to rapidly assess the temporal requirements and phenotypic reversibility of NDD risk gene orthologs using a conditional protein degradation system and machine-vision phenotypic profiling in Caenorhabditis elegans. We measured how degrading and re-expressing orthologs of EBF3, BRN3A and DYNC1H1 at multiple periods throughout development affect 30 morphological, locomotor, sensory and learning phenotypes. We found that phenotypic reversibility was possible for each gene studied. However, the temporal requirements of gene function and degree of rescue varied by gene and phenotype. This work highlights the critical need to assess multiple windows of degradation and re-expression and a large number of phenotypes to understand the many roles a gene can have across the lifespan. This work also demonstrates the benefits of using a high-throughput model system to prioritize NDD risk genes for re-expression studies in other organisms.


Assuntos
Proteínas de Caenorhabditis elegans , Transtornos do Neurodesenvolvimento , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Longevidade , Transtornos do Neurodesenvolvimento/genética , Fenótipo
18.
BMC Med Genomics ; 15(1): 78, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379233

RESUMO

BACKGROUND: Homozygous or compound heterozygous PRUNE1 mutations cause a neurodevelopmental disorder with microcephaly, hypotonia, and variable brain malformations (NMIHBA) (OMIM #617481). The PRUNE1 gene encodes a member of the phosphoesterase (DHH) protein superfamily that is involved in the regulation of cell migration. To date, most of the described mutations in the PRUNE1 gene are clustered in DHH domain. METHODS: We subjected 4 members (two affected and two healthy) of a consanguineous Iranian family in the study. The proband underwent whole-exome sequencing and a start loss identified variant was confirmed by Sanger sequencing. Co-segregation of the detected variant with the disease in family was confirmed. RESULTS: By whole-exome sequencing, we identified the a start loss variant, NM_021222.3:c.3G>A; p.(Met1?), in the PRUNE1 in two patients of a consanguineous Iranian family with spastic quadriplegic cerebral palsy (CP), hypotonia, developmental regression, and cerebellar atrophy. Sanger sequencing confirmed the segregation of the variant with the disease in the family. Protein structure analysis also revealed that the variant probably leads to the deletion of DHH (Asp-His-His) domain, the active site of the protein, and loss of PRUNE1 function. CONCLUSION: We identified a start loss variant, NM_021222.3:c.3G>A; p.(Met1?) in the PRUNE1 gene in two affected members as a possible cause of NMIHBA in an Iranian family. We believe that the study adds a new pathogenic variant in spectrum of mutations in the PRUNE1 gene as a cause of PRUNE1-related syndrome.


Assuntos
Microcefalia , Transtornos do Neurodesenvolvimento , Encéfalo/patologia , Consanguinidade , Humanos , Irã (Geográfico) , Microcefalia/genética , Microcefalia/patologia , Hipotonia Muscular/genética , Hipotonia Muscular/patologia , Transtornos do Neurodesenvolvimento/patologia , Linhagem
19.
BMC Med Genomics ; 15(1): 79, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379245

RESUMO

Genes associated with specific neurocognitive phenotypes in Williams-Beuren syndrome are still controversially discussed. This study identified nine patients with atypical deletions out of 111 patients with Williams-Beuren syndrome; these deletions included seven smaller deletions and two larger deletions. One patient had normal neurodevelopment with a deletion of genes on the distal side of the Williams-Beuren syndrome chromosomal region, including GTF2I and GTF2IRD1. However, another patient retained these genes but showed neurodevelopmental abnormalities. By comparing the genotypes and phenotypes of patients with typical and atypical deletions and previous reports in the literature, we hypothesize that the BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS.


Assuntos
Transtornos do Neurodesenvolvimento , Síndrome de Williams , Receptores Frizzled , Genótipo , Humanos , Transtornos do Neurodesenvolvimento/genética , Fenótipo , Sintaxina 1 , Fatores de Transcrição/genética , Síndrome de Williams/genética , Síndrome de Williams/psicologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-35409689

RESUMO

Autism Spectrum Disorder (ASD) is characterized by deficits in social skills and specific behaviors and interests. Among other environmental factors, iron may play a role in the development of ASD. The aim of this study is to compare the iron status of children with ASD with that of children affected by neurodevelopmental disorders other than ASD (OND). A total of 167 patients were enrolled, including 93 children with ASD and 74 children with OND. In the two groups, we determined ferritin, iron, transferrin, hemoglobin, HCT, and MCV in the serum. We found a significant difference in serum ferritin and MCV levels between the two groups (p < 0.05), with lower ferritin and higher MCV values in the ASD group. There was no significant association with the other variables. Our results may support the hypothesis of altered iron status in ASD, justifying more frequent examinations of blood iron parameters in these children.


Assuntos
Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Transtorno do Espectro Autista/complicações , Criança , Ferritinas , Humanos , Ferro , Dados Preliminares
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...