Subject(s)
Autistic Disorder/genetics , Calcium Channels, L-Type/genetics , Cardiomyopathies/genetics , Gain of Function Mutation/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Long QT Syndrome/genetics , Syndactyly/genetics , Adolescent , Autistic Disorder/diagnostic imaging , Autistic Disorder/physiopathology , Base Sequence , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/physiopathology , Child, Preschool , Electrocardiography , Electrophysiological Phenomena , Humans , Long QT Syndrome/diagnostic imaging , Long QT Syndrome/physiopathology , Syndactyly/diagnostic imaging , Syndactyly/physiopathologyABSTRACT
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.
Subject(s)
Arrhythmias, Cardiac/genetics , Arrhythmogenic Right Ventricular Dysplasia/genetics , Desmoplakins/genetics , Genetic Predisposition to Disease , Arrhythmias, Cardiac/pathology , Arrhythmogenic Right Ventricular Dysplasia/pathology , Female , Genetic Variation , Heart Ventricles/pathology , Humans , Male , Mutation, Missense/genetics , PhenotypeABSTRACT
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.
