Assuntos
Doenças Musculares/complicações , Doenças Musculares/genética , Lipofuscinoses Ceroides Neuronais/complicações , Lipofuscinoses Ceroides Neuronais/genética , Feminino , Humanos , Imageamento por Ressonância Magnética , Glicoproteínas de Membrana/genética , Microscopia Eletrônica de Transmissão , Chaperonas Moleculares/genética , Doenças Musculares/diagnóstico por imagem , Mutação/genética , Lipofuscinoses Ceroides Neuronais/diagnóstico por imagem , Vacúolos/patologia , Vacúolos/ultraestrutura , Adulto JovemRESUMO
Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
Assuntos
Transtornos Mentais/genética , Proteínas do Tecido Nervoso/metabolismo , Transtornos do Neurodesenvolvimento/genética , Proteínas/genética , Adolescente , Adulto , Animais , Transtorno Autístico/genética , Transtorno Autístico/psicologia , Comportamento Animal , Encéfalo/metabolismo , Criança , Pré-Escolar , Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/psicologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Epilepsia/genética , Feminino , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/psicologia , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos do Desenvolvimento da Linguagem/psicologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transtornos Mentais/psicologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mutação , Transtornos do Neurodesenvolvimento/psicologia , Neuroglia/metabolismo , Neurônios/metabolismo , Proteínas/metabolismo , Sequenciamento do Exoma , Adulto JovemAssuntos
Neoplasias da Mama/patologia , Mamilos/patologia , Pólipos/patologia , Complicações Neoplásicas na Gravidez/patologia , Esclerose Tuberosa/complicações , Adulto , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Causalidade , Suscetibilidade a Doenças , Feminino , Humanos , Pólipos/complicações , Pólipos/diagnóstico , Gravidez , Complicações Neoplásicas na Gravidez/diagnósticoRESUMO
PURPOSE: The 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome, is a rare genetic disorder characterized by hypotonia, severely impaired development of speech and language, autistic-like behaviour, and minor dysmorphic features. Neurologic problems may include seizures of different types, such as febrile, generalized tonic-clonic, focal, and absence seizures. No peculiar EEG features have been associated with 22q13 deletion syndrome to date. In order to verify if a peculiar clinical and EEG pattern is present in 22q13.3 deletion syndrome, we studied six Italian patients with this chromosome abnormality. METHOD: Array CGH analysis was carried out in the six subjects (1 male, 5 females, age range 11-30 years, median 19.5). They underwent a complete general and neurologic examinations. The EEG study consisted of at least one awake and one nap-sleep video-EEG recordings and evaluation of other EEGs performed elsewhere. RESULTS: Three subjects suffered from myoclonic or generalized tonic-clonic seizures with a rather benign course; all showed multifocal paroxysmal abnormalities on EEG recording, predominant over the frontal-temporal regions, activated during sleep. CONCLUSION: 22q13.3 deletion syndrome seems to be associated, at least in a subgroup of patients, with a peculiar clinical and EEG pattern, characterized by a childhood epilepsy with a rather benign evolution and with multifocal paroxysmal EEG abnormalities activated by sleep.
Assuntos
Ondas Encefálicas/fisiologia , Transtornos Cromossômicos/complicações , Convulsões/etiologia , Adolescente , Adulto , Criança , Deleção Cromossômica , Transtornos Cromossômicos/patologia , Cromossomos Humanos Par 22 , Eletroencefalografia , Feminino , Humanos , Itália , Masculino , Adulto JovemRESUMO
We report the case of a girl with Cowden syndrome (CS) presenting with unilateral perisylvian dysplasia and with drug resistant focal seizures carrying a novel missense mutation 385G>A (G129R) in the PTEN gene. CS has been rarely reported in association with a cortical malformation or epilepsy. These cases suggest that cortical dysplasia needs to be suspected when a CS patient presents with drug-resistant seizures.