RESUMO
Mutations in SPATA5 have recently been shown to result in a phenotype of microcephaly, intellectual disability, seizures, and hearing loss in childhood. Our aim in this report is to delineate the SPATA5 syndrome as a clinical entity, including the facial appearance, neurophysiological, and neuroimaging findings. Using whole-exome sequencing and Sanger sequencing, we identified three children with SPATA5 mutations from two families. Two siblings carried compound heterozygous mutations, c.989_991del (p.Thr330del) and c.2130_2133del (p.Glu711Profs*21), and the third child had c.967T>A (p.Phe323Ile) and c.2146G>C (p.Ala716Pro) mutations. The three patients manifested microcephaly, psychomotor retardation, hypotonus or hypertonus, and bilateral hearing loss from early infancy. Common facies were a depressed nasal bridge/ridge, broad eyebrows, and retrognathia. Epileptic spasms or tonic seizures emerged at 6-12 months of age. Interictal electroencephalography showed multifocal spikes and bursts of asynchronous diffuse spike-wave complexes. Augmented amplitudes of visually evoked potentials were detected in two patients. Magnetic resonance imaging revealed hypomyelination, thin corpus callosum, and progressive cerebral atrophy. Blood copper levels were also elevated or close to the upper normal levels in these children. Clinical delineation of the SPATA5-related encephalopathy should improve diagnosis, facilitating further clinical and molecular investigation.
Assuntos
Encefalopatias/genética , Proteínas de Homeodomínio/genética , Deficiência Intelectual/genética , Convulsões/genética , Espasmos Infantis/genética , ATPases Associadas a Diversas Atividades Celulares , Agenesia do Corpo Caloso , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/fisiopatologia , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Mutação , Fenótipo , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Espasmos Infantis/diagnóstico por imagem , Espasmos Infantis/fisiopatologiaAssuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Transtornos do Despertar do Sono/induzido quimicamente , Triazinas/efeitos adversos , Adolescente , Anticonvulsivantes/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Humanos , Lamotrigina , Masculino , Convulsões/induzido quimicamente , Triazinas/administração & dosagemRESUMO
We have utilized a gene from bacteriophage T3 that encodes the enzyme S-adenosylmethionine hydrolase (SAMase) to generate transgenic tomato plants that produce fruit with a reduced capacity to synthesize ethylene. S-adenosylmethionine (SAM) is the metabolic precursor of 1-aminocyclopropane-1-carboxylic acid, the proximal precursor to ethylene. SAMase catalyzes the conversion of SAM to methylthioadenosine and homoserine. To restrict the presence of SAMase to ripening fruit, the promoter from the tomato E8 gene was used to regulate SAMase gene expression. Transgenic tomato plants containing the 1.1 kb E8 promoter bore fruit that expressed SAMase during the breaker and orange stage of fruit ripening and stopped expression after the fruit fully ripened. Plants containing the 2.3 kb E8 promoter expressed SAMase at higher levels during the post-breaker phases of fruit ripening and had a substantially reduced capacity to synthesize ethylene.