Smith-Lemli-Opitz syndrome - Fetal phenotypes with special reference to the syndrome-specific internal malformation pattern.

Autosomal-recessive SLOS is caused by mutations in the DHCR7 gene. It is defined as a highly variable complex of microcephaly with intellectual disability, characteristic facies, hypospadias, and polysyndactyly. Syndrome diagnosis is often missed at prenatal ultrasound and fetal autopsy METHODS: We performed autopsies and DHCR7 gene analyses in eight fetuses suspected of having SLOS and measured cholesterol values in long-term formalin-fixed tissues of an additional museum exhibit RESULTS: Five of the nine fetuses presented classical features of SLOS, including four cases with atrial/atrioventricular septal defects and renal anomalies, and one with additional bilateral renal agenesis and a Dandy-Walker cyst.

A small, portable RNA device for the control of exon skipping in mammalian cells.

Splicing is an essential and highly regulated process in mammalian cells. We developed a synthetic riboswitch that efficiently controls alternative splicing of a cassette exon in response to the small molecule ligand tetracycline. The riboswitch was designed to control the accessibility of the 3' splice site by placing the latter inside the closing stem of a conformationally controlled tetracycline aptamer.

Acanthocytosis and the c.680 A>G Mutation in the PANK2 Gene: A Study Enrolling a Cohort of PKAN Patients from the Dominican Republic.

Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). Pantothenate kinases catalyze the rate-limiting step of coenzyme A synthesis and Pank2 is the only pantothenate kinase isoform in humans that is localized to mitochondria. Acanthocytosis, the occurrence of spiculated erythrocytes, is observed in about 10% of the PKAN patients.

Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells.

Rationale: The developmental role of the H3K27 demethylases Jmjd3, especially its epigenetic regulation at target genes in response to upstream developmental signaling, is unclear.

Objective: To determine the role of Jmjd3 during mesoderm and cardiovascular lineage commitment.

Methods And Results: Ablation of Jmjd3 in mouse embryonic stem cells does not affect the maintenance of pluripotency and self-renewal but compromised mesoderm and subsequent endothelial and cardiac differentiation.

Klinefelter twins presenting with discordant aneuploidies, acardia, forked umbilical cord and with different gonadal sex despite monozygosity.

Objective: A higher frequency of twin births in sibships of Klinefelter syndrome patients and also monozygotic or dizygotic twins, themselves being affected by Klinefelter syndrome have been noted repeatedly. To address this issue, we evaluated type and frequency of twinning among Klinefelter fetuses that we had received for autopsy within a 'Prenatal Diagnosis' program.

Method: We performed fetal autopsies, and genetic analyses on DNA extracted from stained histological slides.

Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene.

We report on three hydropic fetuses of 17, 22 and 25 gestational weeks from three distinct families presenting with Desbuquois dysplasia type 1. All fetuses showed brachymelia and characteristic dysmorphic features. X-ray studies revealed δ-shaped extraphalangeal bones and disease-specific prominence of the lesser trochanter, varying in severity with fetal age.

Variations of frataxin protein levels in normal individuals.

Friedreich's ataxia (FRDA) is the most common of the inherited ataxias and is associated with GAA trinucleotide repeat expansions within the first intron of the frataxin (FXN) gene. There are expanded FXN alleles from 66 to 1,700 GAA·TTC repeats in FRDA patients and correlations between number of GAA repeats and frataxin protein levels are assumed. Here, we present for the first time frataxin protein levels as well as analysis of GAA triplet repeats in the FXN gene in a population of 50 healthy Austrian people.

DNA repair polymorphisms associated with cytogenetic subgroups in B-cell chronic lymphocytic leukemia.

Genetic polymorphisms in DNA repair genes can affect the risk of developing different forms of cancer. Therefore, we have studied the putative association of seven single nucleotide polymorphisms (SNPs) in five DNA repair genes with the incidence of chronic lymphocytic leukemia (CLL). We included 461 CLL patients and the same number of age- and sex-matched controls.

Determination of the minimal distance between the matrix and transmembrane domains of the large hepatitis B virus envelope protein.

The cytosolic matrix domain (MD) located between amino acids (aa) 103 and 124 of the large hepatitis B virus envelope protein L is essential for virion formation. We reduced the distance between MD and the transmembrane domain (TD; aa 254 to 272) by deletions starting at aa 132. Six mutants with deletions of up to aa 234 were wild type, and four mutants with slightly larger deletions were blocked with respect to virion morphogenesis.

Volumetric evaluation of the ischemic lesion size with serial MRI in a transient MCAO model of the rat: comparison of DWI and T1WI.

Magnetic resonance imaging (MRI) is applied in many studies on experimental cerebral ischemia in rodents to monitor the temporal evolution of ischemic damage. We report a protocol to evaluate the infarct size after middle cerebral artery occlusion with reperfusion (MCAO/R) in male Wistar rats. Imaging was performed with a 2.

MMP-9 polymorphisms are not associated with spontaneous cervical artery dissection.

Background And Purpose: Cervical artery dissection (CAD) is a common cause of ischemic stroke in young adults. Alteration in the structure of the vascular extracellular matrix has been described in CAD. Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and can lead to vascular damage.

Topographically graded postischemic presence of metalloproteinases is inhibited by hypothermia.

To test the hypothesis that presence of metalloproteases (MMPs), their inhibitors (TIMPs) and their substrate laminin-5 differs between the ischemic core and the surrounding tissue, we examined the impact of middle cerebral artery occlusion/reperfusion (MCA:O/R) on these molecules in different regions of the infarct. We also investigated the influence of hypothermia on the progression of the ischemic lesion and MMP activity. Brain sections from 64 Wistar rats subjected to MCA:O/R were examined by means of cytohistochemistry and zymography.