Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants.

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

Experimental characterization and morphology investigation of composites based on high-density and low-density polyethylene reinforced with non-crimp-stitched glass fabrics

In this study, the effects of matrix material on mechanical properties were investigated in glass fiber reinforced high-density and low-density polyethylene composites. Also, in order to compare the fiber configuration effect on anisotropic behavior, unidirectional and biaxial glass fabrics were used as reinforcement material. Composite laminates were manufactured via the compression molding technique. Tensile and three-point bending flexural tests were conducted up to failure on specimens cut out in different directions. Extensive fracture photomicrographs were presented for observing the failure modes (e.g. delamination) of the composites resulting from a variety of loading conditions. In addition, Scanning electron micrographs of postfractured surfaces of composites were interpreted in an attempt to explain the failure mechanisms (adhesive or cohesive failure) of the composites

Effects of pentoxifylline and platelet activating factor on sperm DNA damage

WOS: 000371187300024PubMed ID: 26748389Objective: Pentoxifylline and platelet-activating factor (PAF) have been used to increase sperm motility in embryology laboratories. In the present study, we aimed to investigate whether these agents pose sperm DNA damage using DNA sperm chromatin dispersion (SCD) assay. Study design: Following application of pentoxifylline and PAF, sperm samples of 50 individuals with different sperm parameters were compared to baseline in terms of DNA damage using SCD assay. Furthermore, the relationship between DNA damage and sperm parameters in predicting DNA damage was assessed. Results and conclusions: Significant increase in DNA damage was observed following application of PAF and pentoxifylline. Furthermore, DNA damage was significantly increased with application of pentoxifylline compared to PAF. Sperm motility was observed to be a statistically significant indicator in predicting alterations in DNA damage in baseline and subsequent to application of PAF and pentoxifylline independent of sperm concentration and morphology. Increased DNA damage was observed in both groups following application of pentoxifylline and PAF. Furthermore, the increase in DNA damage was higher in samples treated with pentoxifylline compared to samples treated with PAF. Thus, PAF seems to be more innocent in choosing viable sperm cells and in achieving sperm motility in the in vitro fertilization laboratory. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Istanbul Bilim University Faculty of Medicine BAPKO ProjectIstanbul Bilim University Faculty of Medicine BAPKO Project

Mandibuloacral dysplasia and LMNA A529V mutation in Turkish patients with severe skeletal changes and absent breast development

WOS: 000378613800001PubMed ID: 27100822Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized by acroosteolysis (resorption of terminal phalanges), skin changes (hyperpigmentation), clavicular hypoplasia, craniofascial anomalies, a hook nose and prominent eyes, delayed closures of the cranial sutures, lipodystrophy, alopecia, and skeletal anomalies. MAD patients are classified according to lipodystrophy patterns: type A and type B. The vast majority of MAD cases are caused by LMNA gene mutations. MAD patients with type A lipodystrophy (MADA) have been reported to have LMNA R527H, A529V, or A529T mutations. In this report, we describe two MADA patients with progressive skeletal changes, absent breast development, and cataract in addition to the classical MAD phenotype. Both patients were found to be homozygous for the Ala529Val mutation of the LMNA gene. Our female patient is the oldest MADA patient (59 years old) who has ever been reported with the LMNA mutation and also the LMNA Ala529Val mutation. This study is the second report on MADA patients with a homozygous Ala529Val mutation

First successful preimplantation genetic diagnosis of epidermolysis bullosa with pyloric atresia: Case study of a novel c.4505-4508insACTC mutation

WOS: 000302070800013PubMed ID: 22354727

False negative QF-PCR and trisomy 18-trisomy 9 mosaicism Yanliş negati̇f QF-PCR ve tri̇zomi̇ 18-tri̇zomi̇ 9 mozai̇zma

Using QF-PCR for rapid prenatal diagnosis of major chromosome aneuploidies demonstrated that the method is highly efficient, reliable and cost effective in the literature. A discrepancy has been showed between QF-PCR and karyotyping results as 0.2% in mosaicism.Our case was in 17 th gestational week who referred to our clinic for having a trisomy 18 risk as 1 in 50 in triple test.On the ultrasonography, we detected bilateral choroid plexus cysts and bilateral pyelectasia.After amniocentesis QF-PCR has been showed a normal chromosomal patern and cytogenetic analysis has been showed trisomy 18 and trisomy 9 mosaicism

A FALSE NEGATIVE QF-PCR AND TRISOMY 18-TRISOMY 9 MOSAICISM

Using QF-PCR for rapid prenatal diagnosis of major chromosome aneuploidies demonstrated that the method is highly efficient, reliable and cost effective in the literature. A discrepancy has been showed between QF-PCR and karyotyping results as 0.2% in mosaicism. Our case was in 17 th gestational week who referred to our clinic for having a trisomy 18 risk as 1 in 50 in triple test. On the ultrasonography, we detected bilateral choroid plexus cysts and bilateral pyelectasia. After amniocentesis QF-PCR has been showed a normal chromosomal patern and cytogenetic analysis has been showed trisomy 18 and trisomy 9 mosaicism