The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype

neurogenetics - Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy with a prevalence of 1 in 2500 individuals worldwide. Here, we report three Turkish siblings from...     

Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.     

Ligneous periodontitis and gingival antioxidant status: report of two cases.

Ligneous periodontitis (LP) is a rare periodontal disease in which plasminogen deficiency and fibrin deposition both play a part, resulting in characteristic gingival enlargement and periodontal breakdown. Recent data suggest that oxidant/antioxidant changes are significant in the pathology of oral diseases. This study examines the gingival histopathology in 2 cases with LP. To examine the antioxidant (AO) status, the activity of the major AOs glutathione (GSH), catalase (CAT), and glutathione S-transferase (GST) and the malondialdehyde (MDA) levels, a product of lipid peroxidation, were measured and compared with healthy control subjects. The histopathologic examination of the gingiva revealed subepithelial fibrin accumulation and irregular extensive downward proliferation of the epithelium. Biochemical analysis showed that the CAT, GST, and MDA levels were higher in LP patients than in the control subjects, and the GSH level was lower. Our preliminary findings show that in LP, the AO capacity of the gingiva changes or decreases and lipid peroxidation increases, which suggests that oxidative stress is involved in the pathology of the periodontal breakdown observed in this disease.     

Survival rates during the first trimester of multiple gestations achieved by ICSI: a report of 1448 consecutive multiples

BACKGROUND: The purpose of this study was to determine the rate of spontaneous gestational sac loss during the first trimester in women achieving multiple pregnancies by ICSI. METHODS: A retrospective analysis was performed of 1448 consecutive multiple pregnancies conceived by ICSI. RESULTS: Of the cohort of 1448 pregnancies, twin gestations constituted 59.6% (864), triplets 30.2% (438) and quadruplets 10.0% (146). During the first trimester, 69 (4.7%) patients miscarried, while 179 (12.3%) continued their pregnancies and had fewer gestational sacs at the end of the first trimester than at the beginning. The overall loss rate of any gestational sac during the first trimester in these multiple pregnancies was 10.1%. There was a significant difference in the frequency of spontaneous reduction to twin or singleton pregnancies in the first trimester between women carrying triplets (11.7%) and those carrying quadruplets (3.5%) [P = 0.004; odds ratio (OR) 3.5; 95% confidence interval (CI) 1.3-9.1]. The frequency of gestational sac loss was significantly greater among women >35 years old (20.9%) than in women less than 35 years old (15.9%) (P = 0.03; OR 1.4; 95% CI 1.0-1.9). CONCLUSION: In multiple pregnancies there is a significant risk of spontaneous loss of any embryo during the first trimester. These findings should be considered prior to any decision about selective embryo reduction.     

Molecular Characterization of a Full Genome Turkish Hepatitis C Virus 1b Isolate (HCV-TR1): A Predominant Viral Form in Turkey

Based on direct sequencing information from 5UTR and NS5B regions, we identified subtype 1b as a predominant hepatitis C virus genome in Turkey, which affected more than 91% of 79 patients studied. Next, the full genome sequence of a Turkish 1b isolate was obtained by the cloning of polypeptide-encoding region into 7 overlapping fragments. Turkish 1b isolate, which was named HCV-TR1, comprises 9361 nucleotides, including 306 nucleotides of 5UTR, a single long open reading frame of 9033 nucleotides, and 22 nucleotides of 3UTR. When compared to HCV 1b polypeptide sequences available at GenBank, the predicted polypeptide displayed a total of 36 amino acid substitutions, of which 16 was specific for HCV-TR1 isolate. Despite these changes, major structural and functional motifs of HCV proteins were maintained in HCV-TR1. In contrast, HCV-TR1 displayed amino acid substitutions in 6 out of 9 major cytotoxic T-cell epitopes. These data suggest that HCV-TR1 encodes functionally intact viral proteins, but it also encodes altered viral epitopes, which may affect host immune-response.     

A randomized trial of ceftriaxone versus trimethoprim-sulfamethoxazole to prevent ventriculoperitoneal shunt infection.

BACKGROUND AND PURPOSE: Shunt infection represents a particularly morbid condition, which can also result in mortality. In order to decrease the high morbidity and mortality rates, prevention is an essential step. The purpose of this study was to compare the prophylactic use of ceftriaxone and trimethoprim-sulfamethoxazole (SXT) for the prevention of ventriculoperitoneal (VP) shunt infection. METHODS: In this prospective, single-institution, randomized clinical trial, 107 children with hydrocephalus and an indication for shunting were randomly assigned to prophylaxis with ceftriaxone (n = 50) or SXT (55), each administered as a single dose during anesthesia and two divided doses postoperatively. Patients were followed up for at least one year. RESULTS: The mean age of patients was 15 months, and 85% were aged 6 months or younger. During the first postoperative year, meningitis occurred in 13.5% of patients receiving ceftriaxone and 14.5% of the SXT group, with no statistically significant difference between the groups. Younger age, presence of cerebrospinal fluid leakage and aqueductal stenosis as a cause of hydrocephalus showed significant correlation with meningitis occurrence on univariate analysis. However, only the latter 2 factors were associated with meningitis on multivariate analysis. The risk of shunt infection did not correlate with the gender of the patient, time of VP shunt surgery, or duration of hospitalization for shunting. CONCLUSION: Ceftriaxone and SXT showed similar efficacy in preventing shunt infection. Cerebrospinal fluid leakage before or after VP shunt placement and aqueductal stenosis were independent risk factors for meningitis after VP shunt.     

Echocardiographically documented mitral-valve prolapse. Long-term follow-up of 237 patients

We determined the long-term prognosis for patients with mitral-valve prolapse documented by echocardiography by following 237 minimally symptomatic or asymptomatic patients for a mean of 6.2 years (range, 1 to 10.4). The actuarial eight-year probability of survival was 88 per cent, which is not significantly different from that for a matched control population. An initial left ventricular diastolic dimension exceeding 60 mm was the best echocardiographic predictor of the subsequent need for mitral-valve replacement (17 patients). Of the 97 patients with redundant mitral-valve leaflets identified echocardiographically, 10 (10.3 per cent) had sudden death, infective endocarditis, or a cerebral embolic event; in contrast, of the 140 patients with nonredundant valves, only 1 (0.7 per cent) had such complications (P less than 0.001). Most patients with echocardiographic evidence of mitral-valve prolapse have a benign course, but subsets at high risk for the development of progressive mitral regurgitation, sudden death, cerebral embolic events, or infective endocarditis can be identified by echocardiography.     

The current perspective on genetic and epigenetic factors in sperm maturation in the epididymis

Male infertility affects approximately 30% of infertile couples. As spermatozoa mature in the epididymal lumen, their potential for mobility increases, and their protein, lipid and small RNA (sRNA) content changes, whereas capacitation and fertilisation take place in the female reproductive tract. Both of the latter processes are affected by maturation, because impaired maturation causes premature capacitation and fertilization. The epididymis produces a suitable environment for sperm maturation via ion transport, vesicle secretion and protein matrix formation. The microenvironment for sperm maturation varies in three broad segments: the caput, the corpus and the cauda epididymis. Epididymosomes transfer proteins, lipids and sRNAs from the epididymal epithelium to spermatozoa and genetic alterations of epididymal genes can lead to decreased sperm motility, morphological abnormalities of spermatozoa and subfertility. Genetic factors are involved in all aetiological categories in male infertility. However, studies conducted on the genes involved in epididymal functions are limited. The sRNA content of spermatozoa changes during epididymal migration, and these sRNAs play a role in embryo development and epigenetic inheritance. This review aims to clarify the role of the epididymal epithelium in the maturation of spermatozoa in light of the current molecular genomic knowledge.     

Communication Patterns Among Male Couples with Open and Monogamous Agreements

Archives of Sexual Behavior - Male couples in open relationships tend to have as equally fulfilling relationships as monogamous male couples; however, less is known about communication differences...     

Bisphosphonate treatment at spondylo-ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Spondylo-ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo-ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles. Previous reports of bisphosphonate treatment response were variable, whereas a long-term follow-up with bisphosphonate treatment in this case resulted in normalization of vertebral structures. Reporting such cases helps to determine the appropriate genotype–phenotype correlation in patients with XYLT2-related pathogenesis.