Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

BACKGROUND AND AIMS: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). METHODS: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. RESULTS AND CONCLUSIONS: From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score 656. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy

High yield preparation of boronic esters of 1,2-diols with lithium trialkylborohydrides

Cyclic boronic esters of 1,2- diols are easily prepared by a new reaction of lithium trialkylborohydrides with 1,2-diols

Synthesis and Solubility Properties of Methanofullerenes Containing Primary Ammonium Ion Functionalities

The synthesis of novel methanofullerene derivatives bearing a primary ammonium ion functionality is described. They are obtained by a Bingel cyclopropanation reaction on C-60 with malonate esters, bearing both a solubilizing poly(oxyethylene) chain and an aliphatic chain ending with a BOC-protected amine. After removal of the protecting group, a counterion exchange methodology allows for the introduction of a perfluorinated anion, bringing the overall solubility of these derivatives to 98 mg/mL in an organic CH2Cl2 solution

Comments on the analysis interpretation by Rogers and Latendresse regarding samples coming from the Shroud of Turin

The presence of a “invisible mending” has been proposed as an explanation for medieval radiocarbon dating measurements made on the Shroud of Turin. Here we show that the chemical analysis which was to support this theory is not consistent, and no scientific data confirm these speculations. Specifically, the samples of the Shroud image fibers underwent a different cleaning procedure with regards to those allegedly belonging to the medieval mending. There is no reliable indication of the supposedly diagnostic compounds (e.g. gum Arabic, pentoses). The only detectable difference between the samples is the presence of a compound with an aliphatic chain which cannot be identified more in detail, e.g. as sebum

There is no mass spectrometry evidence that the C14 sample from the Shroud of Turin comes from a "medieval invisible mending"

This is an editorial regarding a paper published on Thermochimica Acta (R.N. Rogers, Thermochimca Acta, 425 (2005) 189–194). A close-up analysis of the pyrolysis-mass spectra reported in the original paper reveals that the differences found between the samples coming from different parts of the Shroud are just due to the presence of a contaminant with a long aliphatic chain. Except for the presence of the contaminant, the two pyrolysis-mass spectra look alike rather than different. Therefore, the pseudoscientific theory stating that the C14 sample might come from a “medieval invisible mending” remains unsupported by evidences