Infertility affects 12–15% of couples worldwide, and male factors are the cause of nearly half of all cases. Studying seminal fluid composition could lead to additional diagnostic accuracy and a better understanding of the pathophysiology of male factor infertility. Metabolomics offers a new opportunity to evaluate biomarkers and better understand pathological mechanisms. The aim of the study was to identify new markers or therapeutic targets to improve outcomes in male factor or idiopathic infertility patients. Semen samples were obtained from 29 men with a normal spermogram test, and from 18 oligozoospermic men. Samples were processed and analyzed by Nuclear Magnetic Resonance spectroscopy and, subsequently, multivariate and univariate statistical analyses. Receiving Operator Curves (ROC) and Spearman correlations were also performed. An Orthogonal Partial Least Square Discriminant Analysis supervised multivariate model was devised to compare the groups. The levels of fructose, myo-inositol, aspartate and choline were altered. Moreover, Spearman Correlation associated fructose, aspartate and myo-inositol with the total amount of spermatozoa, total motile spermatozoa, % of immotility and % of “in situ” spermatozoic motility respectively. NMR-based metabolomics allowed the identification of a specific metabolic fingerprint of the seminal fluids of patients affected by oligozoospermia.

Genetic testing of myotonic dystrophy type 1 (DM1) is very important because it enables the diagnosis and indicates the severity of the disease. Mutation analysis is based on the detection of the number of CTG triplets in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. Sometimes it could be complicated by the presence of different patterns of repeat interruptions in the 5' and 3' ends of the expanded alleles recently described in about 3% to 5% of patients. To make molecular diagnosis easier and faster, the use of triplet-primed PCR (TP-PCR) for the detection of expansions in DM1 and other dynamic mutation diseases was proposed. Here we present the results of a retrospective study performed by TP-PCR on 100 subjects previously analyzed by Southern blotting-long PCR.

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To the Editor: TMPRSS6 is a transmembrane serine protease expressed mainly in the liver that plays an important role during erythropoiesis. TMPRSS6 loss-of-function mutations result in the over-expression of hepcidin, impaired intestinal iron absorption and ironrefractory iron deficiency anemia (IRIDA). Tmprss6 deletion has been shown to improve iron overload and anemia in murine models of beta-thalassemia intermedia, and the siRNA-or antisense oligonucleotide-mediated suppression of Tmprss6 mRNA expression has been demonstrated to increase the hepcidin level, leading to diminished iron uptake and recycling as well as improved erythropoiesis and anemia in beta thalassemic animals [1,2].TMPRSS6 polymorphisms have been implicated in iron metabolism in both animal and human studies. The common rs855791 polymorphism (NM_153609.3:c.2207C>T) causes a nonsynonymous valine to alanine change (p.V736A), and the T allele (encoding valine) has been associated with lower hemoglobin and ferritin concentrations as well as increased serum transferrin receptor and transferrin concentrations in all populations [3]. Moreover, this polymorphism influences iron overload in hereditary hemochromatosis as well as the development of nonalcoholic fatty liver disease [4,5] and it has been associated with iron deficiency anemia in women of reproductive ages [6].The mechanism of action of TMPRSS6 is still unclear. Some studies have indicated that TMPRSS6 polymorphisms directly affect hepcidin transcription, while others have suggested that the polymorphisms may addictionally influence iron homeostasis by mechanisms independent of hepcidin expression. The latter theory could explain why rs855791 has not been found to be significantly associated with serum hepcidin in some studies [3].In this study, we evaluated the influence of rs855791 on liver iron concentration (LIC) in patients with different levels of ineffective erythropoiesis: mild and severe thalassemia intermedia (TI) and Hemoglobin H (HbH) disease patients, which are clinically distinct forms of the so-called nontransfusion-dependent thalassemias (NTDTs), a term used to label patients who do not require regular transfusion for survival. We classified TI in agreement with the extent of imbalance between the alpha and non alpha globin chains. Accordingly, it was considered as mild in case of coinheritance of heterozygous beta thalassemia and, respectively, triple or quadruple alpha globin gene arrangement, delta/beta 0 thalassemia, and mild or silent beta mutation. It was considered as severe in case of homozygosity or compound heterozygosity for beta 0 mutations.In patients with NTDTs, the increased intestinal absorption of iron caused by ineffective erythropoiesis is the main cause of iron overload, which can become clinically relevant by the age of 10 years. Iron overload is associated with liver dysfunction and vascular, bone, and endocrine morbidities and is therefore an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, although much more rarely tha...

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