Purpose In view of the genetic risks for the next generation, the importance of careful evaluation of karyotypes and AZF microdeletions in male infertility prior to assisted reproduction is evident. In the present study, it is aimed to investigate the frequency and types of both major chromosomal abnormalities by using standard cytogenetic methods and Y chromosome microdeletions of infertile males with azoospermia and oligozoospermia to give appropriate genetic counseling before assisted reproduction techniques in southeast Turkey. Methods A total of 80 infertile males (52 were azoospermic, 25 oligospermic and 3 asthenospermic) were studied for the cytogenetic evaluation and molecular AZF screening program prior to use of assisted reproduction techniques. A detailed history was taken for each man. Karyotyping was performed on peripheral blood lymphocytes according to standard methods. Polymerase chain reaction (PCR) amplification by using 15 Y-specific sequence-tagged sites of AZF region was performed to screen the microdeletions in the AZF region of Y chromosome.

BackgroundNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey.Design and methodsNDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed.ResultsTwenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births.ConclusionsHomozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.

The prevalence of occult HBV infection is not high in haemodialysis patients with chronic HCV in our region. This result of our study has to be evaluated in consideration of the interaction between HBsAg positivity (8%-10%) and frequency of HBV mutants in our region.

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.

The results indicated that the ACE insertion/deletion and angiotensin II type 1 receptor gene polymorphisms were not independent risk factors for renal scar formation in recurrent urinary tract infection of paediatric patients without uropathy.

eterminants of long-term left ventricular (LV) systolic function after myocardial infarction (MI) are related to several factors, including infarct size and location, 1 extension of coronary artery disease (CAD), patency of the infarct-related artery, 2 and the presence of collateral anastomoses to the infarct area. 3 Inhibition of angiotensin-converting enzyme (ACE) also improves postinfarct LV function and survival. 4 The plasma concentration of ACE is mainly genetically determined. The insertion/deletion (ID) polymorphism, located in intron 16 of the ACE gene explains 30-50% of its variance, and also influences the intramyocardial ACE expression. 5,6 Pinto et al have shown that the deletion/deletion (DD) genotype is associated with progressive LV dilatation following a first MI. 7 The prognosis of patients with acute MI is directly related to LV size and systolic function; 8 however, right ventricular (RV) dysfunction after inferior MI is also associated with increased risk of shock, arrhythmias, and death. 9 The Doppler echocardiographic myocardial performance index (MPI), combining time intervals of LV contraction and relaxation, is a powerful predictor of death and congestive heart failure after MI. 10 Noninvasive measurements of time intervals have historically been used for evaluation of both systolic and diastolic function, but because of logistical difficulties in obtaining the intervals, these measure- Circulation Journal Vol.69, February 2005ments have not often been applied clinically. 11 The MPI is obtained by measuring the Doppler time intervals from the mitral inflow, and LV outflow velocity time intervals. This index can be obtained easily, is reproducible and independent of the ventricular geometry, and has been shown to have potential for clinical application in the assessment of overall cardiac function in various disorders. 12,13 Because the combined time intervals in the index also may be obtained from pulsed wave Doppler recordings of the RV inflow and outflow, the manner in which the RVMPI is calculated is similar to that for LVMPI. Moller et al reported that the RVMPI increased in the acute phase of MI, was significantly correlated with indexes of RV systolic dysfunction, and was significantly increased in patients with echocardiographic signs of a RV MI. However, the RVMPI was also considerably higher in patients with no echocardiographic signs of RV MI compared with controls. This may be explained by the fact that an infarction that involves the interventricular septum affects LV function as well as that of the RV, which in theory, produces an increased MPI. 14 The RVMPI correlates with functional class and survival in patients with primary pulmonary hypertension. 14 The relation between ACE gene polymorphism and RVMPI after a first anterior MI has not been reported previously. Therefore the objectives of this study were to investigate the relation between ACE gene polymorphism and RVMPI after a first acute anterior MI. Methods SubjectsWe studied 125 consecutive patients (100 men, 25...

Immunotherapy with specific anti-HBV vaccine in the immune tolerance phase of chronic HBV infection did not offer additional benefit. New immunotherapeutic strategies to control HBV infection by specific HBV vaccines in chronically infected subjects are needed.

ABSTRACT. An insertion/deletion (I/D) polymorphism was identified in intron 16 of the gene encoding the human angiotensin I-converting enzyme (ACE), a candidate gene for chronic obstructive pulmonary disease (COPD). We investigated the relationship between this polymorphism in the ACE gene and the risk of developing COPD. Sixty-six COPD in-patients and 40 non-smoking control individuals were recruited for this study. The distribution of ACE genotypes in these individuals was studied. The frequencies of ACE genotypes were found to be 47.0% for DD, 30.3% for ID, and 22.7% for II in the COPD group and 32.5% for DD, 47.5% for ID, and 20.0% for II in the control group. The allele frequencies were found to be 0.62% for the D allele and 0.38% for the I allele in the COPD group and 0.56% for the D allele and 0.44% for the I allele in the control group. A significant difference ACE gene and chronic obstructive pulmonary disease was found between I and D allele frequencies (P < 0.05) of the study and control groups. Our results suggest that this ACE polymorphism may be associated with the development of COPD.