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OBJECTIVE: PCDH19-related epilepsy occurs predominantly in girls and is caused by pathogenic variant of the protocadherin-19 gene. The initial seizures usually develop in association with fever, begin on average at 15 months of age, and often occur in clusters. Autistic symptoms, intellectual disability, and sleep disturbance are often associated. METHODS: In our retrospective, multicenter study, we reviewed clinical data of nine children with epilepsy genetically confirmed to be associated with PCDH19. RESULTS: In the Hungarian patient population aged 0-18 years, the prevalence of PCDH19-related epilepsy was found to be lower (1/100000 live births in females) than the reported international data (4-5/100000 live births in females). Four of our nine patients had positive family history of epilepsy (cousins, sister, and mother). We assessed brain anomalies in three patients (in one patient focal cortical dysplasia and left anterior cingulate dysgenesis, and in two children right or left hippocampal sclerosis) and in another three cases incidentally identified benign alterations on brain MRI were found. The first seizure presented as a cluster in seven out of nine children. In seven out of nine cases occurred status epilepticus. Six out of nine children had autistic symptoms and only one child had normal intellectual development. Seven of our patients were seizure free with combined antiseizure medication (ASM). The most effective ASMs were levetiracetam, valproate, and clobazam. SIGNIFICANCE: The prevalence of PCDH19-related epilepsy is presumably underestimated because of the lack of widely performed molecular genetic evaluations. Molecular genetic testing including PCDH19 pathogenic variants is recommended for female patients with an onset of seizures before the age of 3 years.
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Though categorized as separate illnesses, schizophrenia and autism are known to exhibit shared characteristics. This study explored the distinctions in clinical, cognitive, and functional characteristics among individuals with recent-onset psychosis, considering the severity of their autistic symptoms, involving longitudinal examinations. We analyzed 671 patients with recent-onset psychosis from Korean Early Psychosis Cohort Study (KEPS), and used the PANSS Autism Severity Score (PAUSS) to categorize patient into 'autistic', 'moderate', and 'non-autistic' groups. The autistic group had the highest rate of schizophrenia diagnosis, and the lowest incidence of comorbid psychiatric disorders. Schizophrenia diagnosis predicted membership of the autistic group. More severe autistic symptoms correlated with worse overall symptoms and functional outcomes, which significantly predicted membership of the autistic group. Cognitive impairments and emotional recognition difficulties increased with the severity of autistic symptoms. 2-year longitudinal assessments demonstrated that group differences in autistic features and overall symptoms, and functional outcomes remained consistent, and membership of the autistic group significantly predicted symptomatic remission and functional recovery. In conclusion, the presence of autistic symptoms has a significant impact on the overall symptomatology and functional capabilities. They are enduring attributes rather than temporary state variables, and serve as a significant predictor for both symptomatic and functional recovery.
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Trastornos Psicóticos , Humanos , Masculino , Femenino , Estudios Longitudinales , Trastornos Psicóticos/fisiopatología , Trastornos Psicóticos/epidemiología , Adulto Joven , Adulto , Trastorno Autístico/fisiopatología , Trastorno Autístico/epidemiología , Esquizofrenia/fisiopatología , Esquizofrenia/epidemiología , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Adolescente , República de Corea/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , ComorbilidadRESUMEN
Dravet syndrome is a severe epileptic encephalopathy, characterized by drug-resistant epilepsy, severe cognitive and behavioural deficits, with increased risk of sudden unexpected death (SUDEP). It is caused by haploinsufficiency of SCN1A gene encoding for the α-subunit of the voltage-gated sodium channel Nav1.1. Therapeutic approaches aiming to upregulate the healthy copy of SCN1A gene to restore its normal expression levels are being developed. However, whether Scn1a gene function is required only during a specific developmental time-window or, alternatively, if its physiological expression is necessary in adulthood is untested up to now. We induced Scn1a gene haploinsufficiency at two ages spanning postnatal brain development (P30 and P60) and compared the phenotypes of those mice to Scn1a perinatally induced mice (P2), recapitulating all deficits of Dravet mice. Induction of heterozygous Nav1.1 mutation at P30 and P60 elicited susceptibility to the development of both spontaneous and hyperthermia-induced seizures and SUDEP rates comparable to P2-induced mice, with symptom onset accompanied by the characteristic GABAergic interneuron dysfunction. Finally, delayed Scn1a haploinsufficiency induction provoked hyperactivity, anxiety and social attitude impairment at levels comparable to age matched P2-induced mice, while it was associated with a better cognitive performance, with P60-induced mice behaving like the control group. Our data show that maintenance of physiological levels of Nav1.1 during brain development is not sufficient to prevent Dravet symptoms and that long-lasting restoration of Scn1a gene expression would be required to grant optimal clinical benefit in patients with Dravet syndrome.
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Epilepsias Mioclónicas , Muerte Súbita e Inesperada en la Epilepsia , Humanos , Ratones , Animales , Canal de Sodio Activado por Voltaje NAV1.1/genética , Epilepsias Mioclónicas/genética , Interneuronas/fisiología , Encéfalo , Mutación , Modelos Animales de EnfermedadRESUMEN
Mutated mito-ribosomal protein S2 (MRPS2) was already described in only three subjects, two with sensorineural hearing impairment, mild developmental delay, hypoglycemia, lactic acidemia and combined oxidative phosphorylation system deficiency and another, recently, presenting with a less severe phenotype. In order to expand the phenotype, we describe a new MRPS2 homozygous subject who shows particular features which have not yet been reported: initial microcephaly, joint hypermobility and autistic features.
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Pérdida Auditiva Sensorineural , Microcefalia , Humanos , Pérdida Auditiva Sensorineural/genética , Microcefalia/genética , Fenotipo , Proteínas Ribosómicas/genéticaRESUMEN
Research shows elevated gender variance among autistic people and more autistic traits among gender diverse people, each of which is related to mental health concerns. Little work has explored broad features of these presentations in a non-clinical sample. College students (n = 174) ages 18-22 years completed questionnaires assessing the broader autism phenotype (BAP), autistic features, nonconformity to gender norms, and internalizing symptoms. Those with more BAP features or autistic communication reported more nonconformity to gender norms. Higher levels of internalizing symptoms were related to more gender nonconformity, BAP, and autistic features. Gender nonconformity marginally moderated the effect of BAP on depression but not anxiety. The BAP, autistic features, and gender nonconformity are important in understanding mental well-being.
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Trastorno del Espectro Autista , Mecanismos de Defensa , Rol de Género , Conformidad Social , Normas Sociales , Estudiantes , Universidades , Estudiantes/psicología , Trastorno del Espectro Autista/psicología , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Análisis de Regresión , Identidad de Género , Encuestas y CuestionariosRESUMEN
ELFN1, a transmembrane leucine rich repeat protein, is involved in signal transduction in both neural cells and ROD ON-bipolar synaptogenesis. We present three siblings with developmental and epileptic encephalopathy and co-morbidities due to ELFN1 gene mutation; this is the first report in literature defining the human phenotype of ELFN1 gene mutation. Clinical, electrophysiological, and radiological findings along with comprehensive genetic studies of the patients and their family members are presented. Developmental and epileptic encephalopathy, autistic features, pyramidal signs, joint laxity, and dysmorphic features are the characteristic findings of this new clinical entity, involving mainly nervous system and possibly connective tissue. Whole exome sequence analysis followed by Sanger sequencing in all family members revealed disease-causing 8 bp frameshift mutation depicted as NM_001128636.2: c.42_49delGGCCGCCA; p. (Ala15Profs*241) in ELFN1. The variant, located in the signal peptide domain in the ELFN1 gene, was found to be homozygous in three patients, and heterozygous in the parents and three healthy siblings. Segregation analysis in family members together with pathogenicity assessment tools strongly supported the damaging effect of the frameshift variant on the function of the ELFN1 protein. Mutations in ELFN1 gene may be considered in patients with neonatal and infantile-onset epileptic encephalopathy before the full clinical picture is apparent.
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Discapacidades del Desarrollo/genética , Inestabilidad de la Articulación/genética , Proteínas del Tejido Nervioso/genética , Espasmos Infantiles/genética , Adolescente , Alelos , Células Cultivadas , Niño , Discapacidades del Desarrollo/patología , Femenino , Mutación del Sistema de Lectura , Homocigoto , Humanos , Lactante , Inestabilidad de la Articulación/patología , Masculino , Proteínas del Tejido Nervioso/metabolismo , Linaje , Fenotipo , Espasmos Infantiles/patologíaRESUMEN
We report heterozygous CELF2 (NM_006561.3) variants in five unrelated individuals: Individuals 1-4 exhibited developmental and epileptic encephalopathy (DEE) and Individual 5 had intellectual disability and autistic features. CELF2 encodes a nucleocytoplasmic shuttling RNA-binding protein that has multiple roles in RNA processing and is involved in the embryonic development of the central nervous system and heart. Whole-exome sequencing identified the following CELF2 variants: two missense variants [c.1558C>T:p.(Pro520Ser) in unrelated Individuals 1 and 2, and c.1516C>G:p.(Arg506Gly) in Individual 3], one frameshift variant in Individual 4 that removed the last amino acid of CELF2 c.1562dup:p.(Tyr521Ter), possibly resulting in escape from nonsense-mediated mRNA decay (NMD), and one canonical splice site variant, c.272-1G>C in Individual 5, also probably leading to NMD. The identified variants in Individuals 1, 2, 4, and 5 were de novo, while the variant in Individual 3 was inherited from her mosaic mother. Notably, all identified variants, except for c.272-1G>C, were clustered within 20 amino acid residues of the C-terminus, which might be a nuclear localization signal. We demonstrated the extranuclear mislocalization of mutant CELF2 protein in cells transfected with mutant CELF2 complementary DNA plasmids. Our findings indicate that CELF2 variants that disrupt its nuclear localization are associated with DEE.
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Proteínas CELF , Epilepsia , Discapacidad Intelectual , Proteínas del Tejido Nervioso , Proteínas CELF/genética , Epilepsia/genética , Femenino , Heterocigoto , Humanos , Discapacidad Intelectual/genética , Proteínas del Tejido Nervioso/genética , Señales de Localización Nuclear/genética , Proteínas de Unión al ARN/genéticaRESUMEN
This study aimed inhibition mechanisms of auditory processing in the group with autistic features. Thirty-two children (autistic group = 16, typically developing [TD] group = 16) received neuropsychological tests, IQ test and experimental tasks. Both groups showed similar performances except the processing speed index. The results showed that the group with autistic features had less inhibition of return (IOR) than the TD group. However, we did not get a statistically significant group difference in the auditory Go-NoGo task. These results might be attributed to a ceiling effect due to an adjustment failure of a difficulty level instead of showing that the group with autistic features would have intact inhibitory or pitch discriminative function problems. In conclusion, this study showed that the group with autistic features could have an inhibitory processing difficulty in both auditory and visual IOR tasks even when their general cognitive functions are relatively intact. This study presented a possibility that the group with autistic features might have a basic inhibitory function problem, but these findings should be investigated in the further study with enough samples. In addition, we are going to revise the auditory Go-NoGo task and verify the feasibility as a tool to detect ASD in an early stage in the following study.
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Percepción Auditiva/fisiología , Trastorno del Espectro Autista/fisiopatología , Inhibición Psicológica , Niño , Femenino , Humanos , Pruebas de Inteligencia , Masculino , Pruebas Neuropsicológicas , Problema de ConductaRESUMEN
We studied three patients with Unverricht-Lundborg disease for autistic features along with other clinical features associated with progressive myoclonus epilepsy. We diagnosed this disease based on noise and touch sensitive myoclonus, ataxia, cognitive decline, typical EEG features, normal MRI of the brain and applied Children's Global Assessment Scale and Childhood Autism Spectrum Test to these children. The CGAS score was 35 in two and 50 in one of them. CAST scores were above 15 in all of three of them. Autistic features may be an important clinical feature of this disease. History and physical examination for myoclonus should probably be taken in autistic children.
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Background Obesity has become one of the greatest health risks worldwide. Recently, there was an explosion of information regarding the role of the central nervous system (CNS) in the development of monogenic and syndromic obesity. Case presentation Over the last decade, terminal and interstitial submicroscopic deletions of copy number variants (CNVs) in 2p25.3 and single nucleotide variants (SNVs) in myelin transcription factor 1 like (MYT1L) were detected by genome-wide array analysis and whole exome sequencing (WES) in patients with a nonspecific clinical phenotype that commonly includes intellectual disability (ID), early onset of obesity and speech delay. Here, we report the first Saudi female patient with mild to moderate ID, early onset of obesity and speech delay associated with a de novo pathogenic SNV in the MYT1L gene (c. 1585G>A [Gly529Arg]), which causes an amino acid change from Gly to Arg at position 529 that leads to mental retardation, autosomal dominant 39.
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Discapacidad Intelectual/etiología , Mutación , Proteínas del Tejido Nervioso/genética , Obesidad/etiología , Factores de Transcripción/genética , Edad de Inicio , Femenino , Humanos , Recién Nacido , Discapacidad Intelectual/patología , Obesidad/patología , PronósticoRESUMEN
Protein tyrosine phosphatase non-receptor type 4 (PTPN4) encodes non-receptor protein tyrosine phosphatase implicated in synaptic plasticity and innate immune response. The only report of PTPN4-associated disease described a neurodevelopmental disorder associated with a whole gene deletion. We describe a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems with a novel mosaic de novo variant in PTPN4 (hg19 chr2:g.120620188 T > C, NM_002830.3:p.[Leu72Ser]/c.215T>C) located in domain that controls protein subcellular distribution. Studies in mouse hippocampal neurons transfected with non-mutated or mutated human PTPN4 showed that despite their similar expression in neurons the mutated protein was absent from dendritic spines. Next, we studied patient's primary blood mononuclear cells' response to lipopolysaccharide stimulation and found no difference from control in phosphorylation of TBK1 and IRF3 (involved in Toll-like receptor 4 signaling) and induction of cytokines' messenger RNA. We conclude that the PTPN4 p.(Leu72Ser) variant is a likely cause of neurodevelopmental symptoms of our proband whereas its role in immune dysfunction requires further studies.
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Espinas Dendríticas/metabolismo , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/genética , Neuronas/metabolismo , Fenotipo , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 4/genética , Alelos , Biomarcadores , Técnica del Anticuerpo Fluorescente , Genes Reporteros , Humanos , Inmunohistoquímica , Masculino , Trastornos del Neurodesarrollo/metabolismo , Transporte de Proteínas , Proteína Tirosina Fosfatasa no Receptora Tipo 4/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Secuenciación del ExomaRESUMEN
RORα, the RAR-related orphan nuclear receptor alpha, is essential for cerebellar development. The spontaneous mutant mouse staggerer, with an ataxic gait caused by neurodegeneration of cerebellar Purkinje cells, was discovered two decades ago to result from homozygous intragenic Rora deletions. However, RORA mutations were hitherto undocumented in humans. Through a multi-centric collaboration, we identified three copy-number variant deletions (two de novo and one dominantly inherited in three generations), one de novo disrupting duplication, and nine de novo point mutations (three truncating, one canonical splice site, and five missense mutations) involving RORA in 16 individuals from 13 families with variable neurodevelopmental delay and intellectual disability (ID)-associated autistic features, cerebellar ataxia, and epilepsy. Consistent with the human and mouse data, disruption of the D. rerio ortholog, roraa, causes significant reduction in the size of the developing cerebellum. Systematic in vivo complementation studies showed that, whereas wild-type human RORA mRNA could complement the cerebellar pathology, missense variants had two distinct pathogenic mechanisms of either haploinsufficiency or a dominant toxic effect according to their localization in the ligand-binding or DNA-binding domains, respectively. This dichotomous direction of effect is likely relevant to the phenotype in humans: individuals with loss-of-function variants leading to haploinsufficiency show ID with autistic features, while individuals with de novo dominant toxic variants present with ID, ataxia, and cerebellar atrophy. Our combined genetic and functional data highlight the complex mutational landscape at the human RORA locus and suggest that dual mutational effects likely determine phenotypic outcome.
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Trastorno Autístico/genética , Ataxia Cerebelosa/genética , Genes Dominantes , Discapacidad Intelectual/genética , Mutación Missense/genética , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Adolescente , Adulto , Anciano de 80 o más Años , Alelos , Animales , Trastorno Autístico/complicaciones , Encéfalo/patología , Ataxia Cerebelosa/complicaciones , Niño , Preescolar , Variaciones en el Número de Copia de ADN/genética , Modelos Animales de Enfermedad , Femenino , Prueba de Complementación Genética , Humanos , Discapacidad Intelectual/complicaciones , Larva/genética , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Células de Purkinje/metabolismo , Células de Purkinje/patología , Síndrome , Pez Cebra/genéticaRESUMEN
Mutations in nuclear receptor SET domain-containing protein 1 gene ( NSD1 ) are related to Sotos syndrome, which is characterized by overgrowth, macrocephaly, distinctive features, and neurodevelopmental disabilities. On the other hand, mutations in the nuclear factor I/X gene ( NFIX ) can lead to Malan syndrome, also known as Sotos-like syndrome, or to the Marshall-Smith syndrome. In this study, using next generation sequencing (NGS), we identified de novo mutations in NSD1 and NFIX in three patients with developmental disabilities associated with overgrowth or macrocephaly. Overall, we confirmed that clinical entities of congenital malformation syndromes can be expanded by molecular diagnoses via NGS.
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Because several genes responsible for epileptic encephalopathy are located on the 9q33q34 region, patients with chromosomal deletions of this region often show intractable epilepsy and neurodevelopmental disability. Contrary to these findings, chromosomal duplications of this region have never been reported previously. We identified a first case of 9q33q34 microduplications in siblings associated with developmental disorders and macrocephaly. Their mother was a mosaic carrier of this duplication. Duplicated regions involved STXBP1; the gene related to epileptic encephalopathy. Neurological features including developmental delay and macrocephaly observed in the present siblings may be derived from the extra-copy of STXBP1.
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Trastornos de los Cromosomas/genética , Duplicación Cromosómica , Cromosomas Humanos Par 9/genética , Discapacidades del Desarrollo/genética , Megalencefalia/genética , Adulto , Niño , Preescolar , Trastornos de los Cromosomas/diagnóstico , Discapacidades del Desarrollo/diagnóstico , Femenino , Heterocigoto , Humanos , Masculino , Megalencefalia/diagnóstico , Mosaicismo , Proteínas Munc18/genética , HermanosRESUMEN
BACKGROUND: Recent studies have indicated an increased risk of autism, behavioural and emotional problems and attention-deficit/hyperactivity disorder in individuals with Down syndrome. METHOD: In a large-scale survey-based study, we examined the rates of these problems and their relationship to age and gender, in a sample of 674 individuals (4-18 years) with Down syndrome. The relationship with IQ level was also explored in a subsample (n = 175). The Strengths and Difficulties Questionnaire and the Social Communication Questionnaire were used to assess behavioural and emotional problems and autism traits. RESULTS: On the Strengths and Difficulties Questionnaire, peer problems were the most frequently reported difficulty (48% > cut-off), followed by hyperactivity/inattention (34% > cut-off). On the Social Communication Questionnaire, 37% scored at or above cut-off (≥15) for autism spectrum disorder; 17% were at or above the suggested cut-off (≥22) for autism. Little association between age and behavioural or emotional problems or with severity of autistic symptomatology was found. However, peer problems were more common in adolescents than in junior school children (P < 0.001); Hyperactivity/inattention was less prevalent among adolescents (P < 0.001). CONCLUSIONS: High rates of autistic features, emotional and behavioural problems are documented. These problems are related to age, gender and degree of intellectual disability.
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Síntomas Afectivos/fisiopatología , Trastorno del Espectro Autista/fisiopatología , Síndrome de Down/fisiopatología , Problema de Conducta , Conducta Social , Adolescente , Síntomas Afectivos/epidemiología , Trastorno del Espectro Autista/epidemiología , Niño , Preescolar , Comorbilidad , Síndrome de Down/epidemiología , Femenino , Humanos , Masculino , Noruega/epidemiología , Reino Unido/epidemiologíaRESUMEN
Many new microdeletion syndromes have been characterized in the past decade, including 2p15-p16.1 microdeletion syndrome. More than 10 patients with this syndrome have been described. Recently, we encountered two additional patients with 2p15-p16.1 microdeletion syndrome. All patients showed variable degrees of intellectual disability, with the autistic features characteristic of this syndrome. Seven out of 16 patients (44%) showed structural abnormalities in the brain, which is also an important feature of this syndrome. The shortest region of microdeletion overlap among the patients includes two genes, USP34 and XPO1. Although these genes have some functional relevance to cancer, they have not been associated with neurological functions. Diagnosis of additional patients with 2p15-p16.1 microdeletion syndrome and identification of pathogenic mutations in this region will help identify the genes responsible for the neurological features of the syndrome.
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Anomalías Múltiples/genética , Encéfalo/patología , Deleción Cromosómica , Cromosomas Humanos Par 2/genética , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hibridación Fluorescente in Situ , Masculino , Fenotipo , Síndrome , Adulto JovenRESUMEN
BACKGROUND: Microdeletion and microduplication syndromes without characteristic dysmorphic features are difficult to diagnose without chromosomal microarrays. PATIENTS: We describe the clinical course and genetic findings of monozygotic twins with intellectual disabilities and autistic features associated with mild facial dysmorphism and microdeletion of chromosome 3p14. RESULTS: The postnatal course of the second twin was complicated by intestinal malrotation, whereas that of the first twin was unremarkable. Both twins had several mild dysmorphic features including upswept frontal hair, low-set posterior rotated ears, arched down-slanting eyebrows, prominent forehead, epicanthic folds, micrognathia, hypertelorism, broad nasal bridge, short philtrum, and camptodactyly of the bilateral fifth fingers. They had autistic features such as poor eye contact and no social smile, stereotyped behaviors, and preference for solitary play. Array comparative genomic hybridization analysis revealed de novo 6.88-Mb deletions of 3p14 (chr3: 60,472,496-67,385,119) involving 17 genes in both twins. The deleted region contained 17 genes, five of which are known or presumed to be related to central nervous system disorders: FEZF2, SYNPR, ATXN7, PRICKLE2, and MAGI1. CONCLUSIONS: We consider that PRICKLE2 is the most likely causative gene for the autistic features exhibited by these individuals.
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Trastorno Autístico/genética , Proteínas con Dominio LIM/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple/genética , Eliminación de Secuencia/genética , Deleción Cromosómica , Cromosomas Humanos Par 3/genética , Humanos , Lactante , Masculino , Gemelos MonocigóticosRESUMEN
Mutations in neuronal voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A may play an important role in the etiology of neurological diseases and psychiatric disorders, besides various types of epilepsy. Here we describe a 3-year-old boy with autistic features, language delay, microcephaly and no history of seizures. Array-CGH analysis revealed an interstitial deletion of ~291.9kB at band 2q24.3 disrupting the entire SCN2A gene and part of SCN3A. We discuss the effects of haploinsufficiency of SCN2A and SCN3A on the genetic basis of neurodevelopmental and neurobehavioral disorders and we propose that this haploinsufficiency may be associated not only with epilepsy, but also with autistic features.
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Anomalías Múltiples/diagnóstico , Trastorno Autístico/diagnóstico , Deleción Cromosómica , Microcefalia/diagnóstico , Canal de Sodio Activado por Voltaje NAV1.2/genética , Canal de Sodio Activado por Voltaje NAV1.3/genética , Trastornos Psicomotores/diagnóstico , Canales de Sodio/genética , Anomalías Múltiples/genética , Trastorno Autístico/genética , Preescolar , Cromosomas Humanos Par 2 , Hibridación Genómica Comparativa , Haploinsuficiencia , Humanos , Trastornos del Desarrollo del Lenguaje/diagnóstico , Trastornos del Desarrollo del Lenguaje/genética , Masculino , Microcefalia/genética , Trastornos Psicomotores/genética , Convulsiones/diagnóstico , Convulsiones/genéticaRESUMEN
An increasing number of patients with 3p proximal deletions were reported in the previous decade, but the region responsible for the main features such as intellectual disability (ID) and developmental delay is not yet characterized. Here we report on two monozygotic twin brothers of 2 10/12 years and an 18-year-old man, all three of them displaying severe ID, psychomotoric delay, autistic features, and only mild facial dysmorphisms. Array CGH (aCGH), revealed a 6.55 Mb de novo interstitial deletion of 3p14.1p14.3 in the twin brothers and a 4.76 Mb interstitial deletion of 3p14.1p14.2 in the 18-year-old patient, respectively. We compared the malformation spectrum with previous molecularly well-defined patients in the literature and in the DECIPHER database (Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources; http://decipher.sanger.ac.uk/). In conclusion, the deletion of a region containing 3p14.2 seems to be associated with a relative concise phenotype including ID and developmental delay. Thus, we hypothesize that 3p14.2 is the potential core region in 3p proximal deletions. The knowledge of this potential core region could be helpful in the genetic counselling of patients with 3p proximal deletions, especially concerning their phenotype.