Assuntos
Transtorno Autístico/genética , Canais de Cálcio Tipo L/genética , Cardiomiopatias/genética , Mutação com Ganho de Função/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Síndrome do QT Longo/genética , Sindactilia/genética , Adolescente , Transtorno Autístico/diagnóstico por imagem , Transtorno Autístico/fisiopatologia , Sequência de Bases , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Pré-Escolar , Eletrocardiografia , Fenômenos Eletrofisiológicos , Humanos , Síndrome do QT Longo/diagnóstico por imagem , Síndrome do QT Longo/fisiopatologia , Sindactilia/diagnóstico por imagem , Sindactilia/fisiopatologiaRESUMO
Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular cardiomyopathies. We present a family with arrhythmogenic cardiomyopathy associated with a novel missense variant in DSP (NM_004415.4): c.877G>A, p.(Glu293Lys). The phenotype is characterized by predominant involvement of the left ventricle with systolic dysfunction, fibrosis, and life-threatening arrhythmias. We performed a systematic review of literature collecting all cardiomyopathy cases with rare missense variants in DSP. We demonstrate that the distribution of missense variants across the protein domains in cardiomyopathy cases differs from that in gnomAD (p = .04), with a case enrichment of rare missense variants in the spectrin repeat domain (36/78 [46%] in cases vs. 449/1495 [30%] in gnomAD; p = .004). Our findings highlight the predominance of cardiac arrhythmia and left ventricular involvement in desmoplakin cardiomyopathy and pinpoint to a potential mutation hotspot in DSP thereby facilitating missense variant interpretation in the diagnostic setting.
Assuntos
Arritmias Cardíacas/genética , Displasia Arritmogênica Ventricular Direita/genética , Desmoplaquinas/genética , Predisposição Genética para Doença , Arritmias Cardíacas/patologia , Displasia Arritmogênica Ventricular Direita/patologia , Feminino , Variação Genética , Ventrículos do Coração/patologia , Humanos , Masculino , Mutação de Sentido Incorreto/genética , FenótipoRESUMO
Little information is available concerning whether incorporation of dietary omega-3 fatty acids into plasma lipids changes during healthy aging. Elderly (74 +/- 4 years old) and young (24 +/- 2 years old) adults were given a fish oil supplement for 3 weeks that provided 680 mg/day of docosahexaenoic acid and 320 mg/day of eicosapentaenoic acid, followed by a 2 week wash-out period. Compliance was monitored by spiking the capsules with carbon-13 glucose, the excretion of which was measured in breath CO2. In response to the supplement, plasma docosahexaenoic acid rose 42% more in the elderly but eicosapentaenoic responded similarly in both groups. Despite raising docosahexaenoic acid intake by five to tenfold, the supplement did not raise plasma free docosahexaenoic acid (% or mg/dL) in either group. We conclude that healthy aging is accompanied by subtle but significant changes in DHA incorporation into plasma lipids.