OBJECTIVE: To better understand the role of lecithin:cholesterol acyltransferase (LCAT) in lipoprotein metabolism through the genetic and biochemical characterization of families carrying mutations in the LCAT gene. METHODS AND RESULTS: Thirteen families carrying 17 different mutations in the LCAT gene were identified by Lipid Clinics and Departments of Nephrology throughout Italy. DNA analysis of 82 family members identified 15 carriers of 2 mutant LCAT alleles, 11 with familial LCAT deficiency (FLD) and 4 with fish-eye disease (FED). Forty-four individuals carried 1 mutant LCAT allele, and 23 had a normal genotype. Plasma unesterified cholesterol, unesterified/total cholesterol ratio, triglycerides, very-low-density lipoprotein cholesterol, and pre-beta high-density lipoprotein (LDL) were elevated, and high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, LpA-I, LpA-I:A-II, cholesterol esterification rate, LCAT activity and concentration, and LDL and HDL3 particle size were reduced in a gene-dose-dependent manner in carriers of mutant LCAT alleles. No differences were found in the lipid/lipoprotein profile of FLD and FED cases, except for higher plasma unesterified cholesterol and unesterified/total cholesterol ratio in the former. CONCLUSIONS: In a large series of subjects carrying mutations in the LCAT gene, the inheritance of a mutated LCAT genotype causes a gene-dose-dependent alteration in the plasma lipid/lipoprotein profile, which is remarkably similar between subjects classified as FLD or FED.
BACKGROUND:
Aim of this study was to investigate the frequency of association between Myasthenia Gravis (MG) and Graves Ophthalmopathy (GO) using the responses to diagnostic tests for MG (fatigue and neostigmine tests) by measuring horizontal saccadic eye movements (SEM).
METHODS:
For this paper a random investigation was performed on eleven patients, affected by Graves' disease (GD) at the department of Molecular and Clinical Endocrinology and Oncology and department of Neurology of University of Federico II of Naples, for one year. Eleven patients (11 F), were subjected to endocrinological and ophthalmological examinations (TSH IRMA, TT3-RIA, TT4-RIA, TgAb, TPOAb, orbit ultrasonography or computed tomographic scans) and computerized analysis of saccadic eye movements (SEM); the fatigue and neostigmine tests were performed by means of SEM analysis in seven of this patients.
RESULTS:
Our results have reported that a positive response to the diagnostic tests for MG is present in 41.6% of hyperthyroid patients with GO, further supporting the hypothesis of a common autoimmune pathogenesis is present between these pathologies.
