RESUMO
Phenotypic features of KBG syndrome include craniofacial anomalies, short stature, cognitive disability and behavioral findings. The syndrome is caused by heterozygous pathogenic single nucleotide variants and indels in ANKRD11, or a heterozygous deletion of 16q24.3 that includes ANKRD11. We performed genome sequencing on a patient with clinical manifestations of KBG syndrome including distinct craniofacial features as well as a history of mild intellectual disability and attention-deficit hyperactivity disorder. This led to the identification of a 43 kb intragenic deletion of ANKRD11 affecting the first noncoding exon while leaving the coding regions intact. Review of the literature shows that this is the smallest 5' deletion affecting only the noncoding exons of ANKRD11. Real-time polymerase chain reaction demonstrated that the copy number variant was not present in either of the proband's parents, suggesting it occurred de novo. RNA expression analysis demonstrated significantly decreased transcript abundance compared to controls. This provides new evidence for haploinsufficiency as a mechanism of disease in KBG syndrome.
Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Deficiência Intelectual , Anormalidades Dentárias , Humanos , Anormalidades Múltiplas/genética , Deficiência Intelectual/genética , Doenças do Desenvolvimento Ósseo/genética , Anormalidades Dentárias/genética , Fácies , Proteínas Repressoras/genética , Deleção Cromossômica , Fatores de Transcrição/genética , FenótipoRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia in elderly ( >65years of age). Excessive extra cellular deposits of amyloid beta (Aß) are a pathological feature of AD. Aß can cause cell death through oxidative damage; recent studies have implicated opening of mPTP as a detrimental event in AD-related mitochondrial dysfunctions. Over the past few years, natural compounds with antioxidant properties have shown promise for intervention in AD.
Assuntos
Peptídeos beta-Amiloides/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Monoterpenos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Espécies Reativas de Oxigênio/metabolismoRESUMO
Cadmium (Cd(2+) ) causes alteration of the cellular homeostasis and oxidative damage. The aim of the present study was to investigate the possible protective role of thymoquinone (TQ), a predominant bioactive component present in black seed oil (Nigella sativa) on the hepatotoxicity of Cd(2+) with special reference to its protection against perturbation of nonenzymatic and enzymatic antioxidants. The effect of TQ pretreatment was examined in postnuclear supernatant prepared from liver of Swiss albino mice under in vitro conditions. CdCl(2) treatment (5 mM) resulted in a significant increase in antioxidant enzymatic activities. It also caused a significant (p < 0.001) increase in protein carbonyl and reduced glutathione content. Pretreatment with TQ (10 µM) showed a significant protection as manifested by noticed attenuation of protein oxidation and rejuvenation of the depleted antioxidants of cellular fraction. These results strengthen the hypothesis that TQ exerts modulatory influence on the antioxidant defense system on being subjected to toxic insult.