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ABSTRACT Background: Fukuyama congenital muscular dystrophy (FCMD) is the most common form of a group of autosomal recessive disorders characterized by altered α-dystroglycan glycosylation and caused by FKTN gene mutations. However, mutations of this gene may cause a broad range of phenotypes, including Walker-Warburg syndrome, muscle-brain-eye disease, FCMD, limb-girdle muscular dystrophy without mental retardation, and cardiomyopathy with no or minimal skeletal muscle weakness. Objective: Our purpose was to describe two siblings who died at a young age with dilated cardiomyopathy (DCM), no muscle weakness, or atrophy, and were homozygous for a FKTN missense mutation. Methods: Site-directed next-generation sequencing (NGS) was performed. Pathogenicity of variants of interest was established according to the American College of Medical Genetics (ACMG) criteria, and all available first-degree relatives were screened for mutations by Sanger sequencing. Results: NGS revealed a homozygous FKTN variant in the index case (p.Gly424Ser, rs752358445), classified as likely pathogenic by ACMG criteria. Both parents and an unaffected brother were heterozygous carriers. Since the siblings had no apparent skeletal muscle weakness or central nervous system involvement, FKTN mutations were not initially suspected. Conclusions: This is the first report demonstrating that heterozygous individuals for the FKTN p.Gly424Ser mutation were healthy, while two homozygous brothers suffered severe DCM, strongly suggesting that this FKTN mutation is a rare cause of autosomal recessive DCM.
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Hypercholesterolemia prompts to endothelial dysfunction (ED) and ED predisposes to atherogenesis. ED appears early in the course of atherogenesis and it is considered a coronary artery disease (CAD) marker. OBJECTIVES: To assess endothelial function (EF) using Positron Emission Tomography (PET) in asymptomatic patients with recent dyslipidemia diagnosis and without history of ischemic heart disease and previous hypolipemiant treatment. MATERIAL AND METHODS: Fourteen asymptomatic patients with recent dyslipidemia diagnosis (< 6 months) were studied by obtaining a lipid profile, blood glucose, and a three phase 13N-ammonia PET scan: rest, cold pressor test (CPT) and pharmacologic stress with adenosine. EF was assessed by calculating the coronary flow reserve (CFR), endothelial-dependant vasodilatation index (EDVI), and coronary blood flow increase percentage in CPT (% Delta CF). RESULTS: 79% of patients with dyslipidemia had ED and all their values were lower than those previously published as normal: rest coronary flow 0.44 +/- 0.12 vs 0.57 +/- 0.147 (p = 0.002), CPT coronary flow 0.57 +/- 0.17 vs 0.88 +/- 0.26 (p = 0.001), stress coronary flow 1.24 +/- 0.05 vs 1.81 +/- 0.35 (p = 0.005), EDVI 1.28 +/- 0.25 vs 1.53 +/- 0.24 (p 0.017), CRF 2.79 +/- 0.94 vs 3.15 +/- 0.48 (p 0.198) and % Delta CF 29.08 +/- 24.62% vs 53 +/- 24.60% (p 0.022). Conclusions: Asymptomatic patients in early stages of dyslipidemia showed a greater ED prevalence that was detected by 13N-ammonia PET scan.