The Australia and New Zealand Fontan Registry: description and initial results from the first population-based Fontan registry.

BACKGROUND: The Fontan procedure is the final in a series of staged palliations for single-ventricle congenital heart disease, which encompasses rare and heterogeneous cardiac lesions. It represents an unusual and novel physiological state characterised by absence of a subpulmonary ventricle. AIMS: The population is growing steadily, prompting creation of this registry to study their epidemiology, demographic trends, treatment and outcomes. METHODS: This multicentre, binational, prospective and retrospective, web-based registry involving all congenital cardiac centres in the region has identified nearly all Fontan patients in Australia and New Zealand. Patients identified retrospectively were approached for recruitment. New recipients are automatically enrolled prospectively unless they choose to opt-out. Follow-up data are collected yearly. RESULTS: Baseline data were obtained in 1072 patients as at 1 January 2011. Ninety-nine patients died; 64 were lost to follow up. Forty-four per cent of patients lost were between 20 and 30 years of age. The size of the Fontan population is increasing steadily. Among 973 living patients, 541 (56%) gave consent for prospective collection of follow up. Between 1 January 2011 and 1 January 2013, an additional 47 subjects were enrolled prospectively. The current proportion of patients operated with hypoplastic left heart syndrome is currently 29% and is growing rapidly. CONCLUSION: The population surviving after the Fontan procedure has been growing in recent decades, especially since survival with hypoplastic left heart syndrome has improved. The Australia and New Zealand Fontan Registry provides population-based data, and only large databases like this will give opportunities for understanding the population and performing prospective trials.

Association of in vitro fertilization with global and IGF2/H19 methylation variation in newborn twins.

In vitro fertilization (IVF) and its subset intracytoplasmic sperm injection (ICSI), are widely used medical treatments for conception. There has been controversy over whether IVF is associated with adverse short- and long-term health outcomes of offspring. As with other prenatal factors, epigenetic change is thought to be a molecular mediator of any in utero programming effects. Most studies focused on DNA methylation at gene-specific and genomic level, with only a few on associations between DNA methylation and IVF. Using buccal epithelium from 208 twin pairs from the Peri/Postnatal Epigenetic Twin Study (PETS), we investigated associations between IVF and DNA methylation on a global level, using the proxies of Alu and LINE-1 interspersed repeats in addition to two locus-specific regulatory regions within IGF2/H19, controlling for 13 potentially confounding factors. Using multiple correction testing, we found strong evidence that IVF-conceived twins have lower DNA methylation in Alu, and weak evidence of lower methylation in one of the two IGF2/H19 regulatory regions and LINE-1, compared with naturally conceived twins. Weak evidence of a relationship between ICSI and DNA methylation within IGF2/H19 regulatory region was found, suggesting that one or more of the processes associated with IVF/ICSI may contribute to these methylation differences. Lower within- and between-pair DNA methylation variation was also found in IVF-conceived twins for LINE-1, Alu and one IGF2/H19 regulatory region. Although larger sample sizes are needed, our results provide additional insight to the possible influence of IVF and ICSI on DNA methylation. To our knowledge, this is the largest study to date investigating the association of IVF and DNA methylation.

Decreased cortical muscarinic M1 receptors in schizophrenia are associated with changes in gene promoter methylation, mRNA and gene targeting microRNA.

Many studies have shown decreased cortical muscarinic M1 receptors (CHRM1) in schizophrenia (Sz), with one study showing Sz can be separated into two populations based on a marked loss of CHRM1 (-75%) in -25% of people (Def-Sz) with the disorder. To better understand the mechanism contributing to the loss of CHRM1 in Def-Sz, we measured specific markers of gene expression in the cortex of people with Sz as a whole, people differentiated into Def-Sz and people with Sz that do not have a deficit in cortical CHRM1 (Non-Def-Sz) and health controls. We now report that cortical CHRM1 gene promoter methylation and CHRM1 mRNA are decrease in Sz, Def-Sz and Non-Def-Sz but levels of the micro RNA (miR)-107, a CHRM1 targeting miR, are increased only in Def-Sz. We also report in vitro data strongly supporting the notion that miR-107 levels regulate CHRM1 expression. These data suggest there is a reversal of the expected inverse relationship between gene promoter methylation and CHRM1 mRNA in people with Sz and that a breakdown in gene promoter methylation control of CHRM1 expression is contributing to the global pathophysiology of the syndrome. In addition, our data argues that increased levels of at least one miR, miR-107, is contributing to the marked loss of cortical CHRM1 in Def-Sz and this may be a differentiating pathophysiology. These latter data continue to support the hypothesis that microRNAs (miRNA) have a role in the underlying neurobiology of Sz but argue they are differentially affected in subsets of people within that syndrome.