RESUMO
BCL11A encodes a zinc finger protein that is highly expressed in hematopoietic tissues and the brain, and that is known to function as a transcriptional repressor of fetal hemoglobin (HbF). Recently, de novo variants in BCL11A have been reported in individuals with intellectual disability syndrome without epilepsy. In this study, we performed whole-exome sequencing of 302 patients with epileptic encephalopathies (EEs), and identified 2 novel BCL11A variants, c.577delC (p.His193Metfs*3) and c.2351A>C (p.Lys784Thr). Both the patients shared major physical features characteristic of BCL11A-related intellectual disability syndrome, suggesting that characteristic physical features and the persistence of HbF should lead clinicians to suspect EEs caused by BCL11A pathogenic variants. Patient 1, with a frameshift variant, presented with Lennox-Gastaut syndrome, which expands the phenotypic spectrum of BCL11A haploinsufficiency. Patient 2, with a p.Lys784Thr variant, presented with West syndrome followed by drug-resistant focal seizures and more severe developmental disability. These 2 newly described patients contribute to delineating the associated, yet uncertain phenotypic characteristics of BCL11A disease-causing variants.
Assuntos
Encefalopatias/genética , Proteínas de Transporte/genética , Epilepsia/genética , Deficiência Intelectual/genética , Proteínas Nucleares/genética , Adolescente , Encefalopatias/fisiopatologia , Criança , Epilepsia/fisiopatologia , Feminino , Mutação da Fase de Leitura/genética , Humanos , Recém-Nascido , Deficiência Intelectual/fisiopatologia , Síndrome de Lennox-Gastaut/genética , Síndrome de Lennox-Gastaut/fisiopatologia , Masculino , Proteínas Repressoras , Espasmos Infantis/genética , Espasmos Infantis/fisiopatologia , Sequenciamento do ExomaAssuntos
Corpos Cetônicos/análise , Ácido 3-Hidroxibutírico , Acetoacetatos/análise , Autoanálise , Compostos de Diazônio , Humanos , Hidroxibutiratos/análise , Corpos Cetônicos/sangue , Corpos Cetônicos/urina , L-Lactato Desidrogenase/antagonistas & inibidores , Lactatos , Microquímica , Ácido Oxâmico , PiruvatosRESUMO
Heritabilities of and genetic correlations between additive direct and maternal genetic effects for calf market weight, and additive direct genetic effects for carcass traits, were estimated for Japanese Black cattle by REML procedures under 2-trait animal models. Data were collected from calf and carcass markets in Hyogo and Tottori prefectures and analyzed separately by prefecture. Calf market weight was measured on 42,745 and 23,566 calves in Hyogo and Tottori, respectively. Only the fattening animals with calf market weight were extracted from the carcass database and used for estimation. The carcass traits analyzed were carcass weight, ribeye area, rib thickness, subcutaneous fat thickness, yield estimate, beef marbling score, and 4 meat characters (color, brightness, firmness, and texture). Direct and maternal heritabilities for calf market weight were estimated to be 0.22 and 0.07 in Hyogo, and 0.37 and 0.15 in Tottori, respectively. The estimates of heritabilities for carcass traits were moderate to high in both prefectures. The estimates of direct-maternal genetic correlations for calf market weight were positive (0.17) in Hyogo and negative (-0.63) in Tottori. The direct effect for calf market weight was positively correlated with the direct effect for carcass weight (0.87 and 0.56 in Hyogo and Tottori, respectively) but negatively correlated with the direct effect for beef marbling score (-0.10 in both prefectures). The estimates of genetic correlations between the maternal effect for calf market weight and the direct effects for carcass traits varied from -0.13 to 0.34 in Hyogo and from -0.14 to 0.15 in Tottori. Because direct and maternal genetic effects for early growth traits can be evaluated from calf market weight data in the production system of Japanese Black cattle, this information should be incorporated into selection and mating schemes of the breed.
Assuntos
Peso Corporal/genética , Bovinos/genética , Variação Genética , Carne/normas , Animais , Cruzamento , Bovinos/fisiologia , Feminino , Japão , Modelos Lineares , Masculino , Modelos Genéticos , FenótipoRESUMO
BACKGROUND: Patients with encephalopathy heralded by a prolonged seizure as the initial symptom often have abnormal subcortical white matter on diffusion-weighted MRI (DWI). OBJECTIVE: To determine if these patients share other common features. METHODS: Patients with encephalopathy heralded by a prolonged seizure and followed by the identification of abnormal subcortical white matter on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Seventeen patients were identified, ages 10 months to 4 years. All had a prolonged febrile seizure (longer than 1 hour in 12 patients) as their initial symptom. Subsequent seizures, most often in clusters of complex partial seizures, were seen 4 to 6 days after the initial seizure in 16 patients. Outcome ranged from almost normal to severe mental retardation. MRI performed within 2 days of presentation showed no abnormality. Subcortical white matter lesions were observed on DWI between 3 and 9 days in all 17 patients. T2-weighted images showed linear high intensity of subcortical U fibers in 13 patients. The lesions were predominantly frontal or frontoparietal in location with sparing of the perirolandic region. The diffusion abnormality disappeared between days 9 and 25, and cerebral atrophy was detected later than 2 weeks. Three patients having only frontal lesions had relatively good clinical outcome. CONCLUSIONS: Although the pathophysiologic mechanism remains unknown, these patients seem to have a distinctive encephalopathy syndrome. MRI is helpful in establishing the diagnosis of this encephalopathy.