http://www.biomedcentral.com/bmcmedgenet/ The editor's pick of recent articles published by BMC Medical Genetics 2012-03-19T00:00:00Z Background: Hypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine.MethodologyIn this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population. Results: HRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations. Conclusions: HRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations. http://www.biomedcentral.com/1471-2350/13/17 Susana Santos Vanda Marques Marina Pires Leonor Silveira Helena Oliveira Vasco Lança Dulce Brito Hugo Madeira J Fonseca Esteves António Freitas Isabel M Carreira Isabel M Gaspar Carolino Monteiro Alexandra R Fernandes BMC Medical Genetics 2012, 13:17 2012-03-19T00:00:00Z 10.1186/1471-2350-13-17 High resolution melting test for HCM High resolution melting can provide a robust, quick and cheap means of genetic testing, demonstrated by application to detect variants linked to Hypertrophic Cardiomyopathy (HCM) in a Portuguese population with high sensitivity and a low false positive rate. /content/figures/1471-2350-13-17-toc.gif BMC Medical Genetics 1471-2350 13 17 2012-03-19T00:00:00Z XML Background: Mucins are highly glycosylated proteins protecting and lubricating epithelial surface of respiratory, gastrointestinal and reproductive tracts. Members of the mucin protein family have been suggested to play an important role in development of endometriosis and infertility. This study investigates genetic association of mucin2 (MUC2) with the risk of endometriosis and endometriosis-related infertility. Methods: This case-control study was conducted at China Medical University Hospital, with 195 endometriosis patients and 196 healthy controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288, rs10902088, rs7103978 and rs11245954) within MUC2 gene were performed by using Taqman genotyping assay; individual SNP and haplotype associations with endometriosis and endometriosis-related infertility were assessed by χ 2 test. Results: Endometriosis patients exhibit significantly lower frequency of the rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (P = 0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and the rs10902088 T allele were also less abundant in patients with infertility versus fertile ones (P = 0.015 and 0.024, respectively). Haplotype analysis of the endometriosis associated SNPs in MUC2 also showed significantly association between the most common haplotypes and endometriosis or endometriosis-related infertility. Conclusions: MUC2 polymorphisms, especially rs10794288 and rs10902088, are associated with endometriosis as well as endometriosis-related infertility. Our data present MUC2 as a new candidate involved in development of endometriosis and related infertility in Taiwanese Han women. http://www.biomedcentral.com/1471-2350/13/15 Cherry Chang Yi Chen Wu-Chou Lin Chih-Mei Chen Chih-Ping Chen Shan-Chih Lee Jim Sheu Fuu-Jen Tsai BMC Medical Genetics 2012, 13:15 2012-03-15T00:00:00Z 10.1186/1471-2350-13-15 MUC2 link to endometriosis In addition to the previously known association with MUC1 and MUC4, polymorphisms in the mucin gene MUC2 are also associated with endometriosis and endometriosis-related infertility in Taiwanese women. /content/figures/1471-2350-13-15-toc.gif BMC Medical Genetics 1471-2350 13 15 2012-03-15T00:00:00Z XML Background: Fragile X syndrome (FXS), the leading cause of inherited mental retardation, is due to expansion and methylation of a CGG sequence in the FMR1 gene, which result in its silencing and consequent absence of FMRP protein. This absence causes loss of repression of metabotropic glutamate receptor 5 (mGluR5)-mediated pathways resulting in the behavioral and cognitive impairments associated with FXS. In a randomized, double-blind trial it was recently demonstrated a beneficial effect of AFQ056, a selective inhibitor of metabotrobic glutamate receptor type 5 (mGluR5), on fully methylated FXS patients respect to partially methylated FXS ones. Methods: To determine whether AFQ056 may have secondary effects on the methylation and transcription of FMR1, here we treated three FXS lymphoblastoid cell lines and one normal control male line. A quantitative RT-PCR was performed to assess transcriptional reactivation of the FMR1 gene. To assess the methylation status of the FMR1 gene promoter it was carried out a bisulphite sequencing analysis. Results: Both FMR1-mRNA levels and DNA methylation were unmodified with respect to untreated controls. Conclusions: These results demonstrate that the AFQ056 effect on fully methylated FXS patients is not due to a secondary effect on DNA methylation and consequent transcriptional activation of FMR1. http://www.biomedcentral.com/1471-2350/13/13 Elisabetta Tabolacci Filomena Pirozzi Baltazar Gomez-Mancilla Fabrizio Gasparini Giovanni Neri BMC Medical Genetics 2012, 13:13 2012-03-07T00:00:00Z 10.1186/1471-2350-13-13 FMR1 gene methylation not targeted by Fragile X drug The beneficial effect of Fragile X syndrome (FXS) drug AFQ056 for patients with fully methylated FMR1 genes does not act through a secondary effects on FMR1 mRNA production or promoter methylation, in FXS lymphoblastoid cell lines. /content/figures/1471-2350-13-13-toc.gif BMC Medical Genetics 1471-2350 13 13 2012-03-07T00:00:00Z XML