Exome sequencing links the SUMO protease SENP7 with fatal arthrogryposis multiplex congenita, early respiratory failure and neutropenia.

Background: SUMOylation involves the attachment of small ubiquitin-like modifier (SUMO) proteins to specific lysine residues on thousands of substrates with target-specific effects on protein function. Sentrin-specific proteases (SENPs) are proteins involved in the maturation and deconjugation of SUMO. Specifically, SENP7 is responsible for processing polySUMO chains on targeted substrates including the heterochromatin protein 1α (HP1α).

Diagnosis of fetal cortical abnormalities by new reference charts for assessment of sylvian fissure biometry.

Objective: To develop novel fetal reference ranges for the characterization of the normal appearance of the Sylvian fissures (SF) along gestation and to apply them to fetuses with cortical abnormalities affecting the SF.

Methods: In this cross-sectional study, we used three-dimensional sonographic multiplanar reformatting (3D-MPR) to examine the fetal SF. Normal development was assessed in the second and third trimesters.

αvβ3 Integrin Expression and Mitogenic Effects by Thyroid Hormones in Chronic Lymphocytic Leukemia.

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The thyroid hormones, T3 and T4, bind the αvβ3 integrin and activate phosphorylates ERK (pERK). These tumor-promoting actions were reported in a number of malignancies, but not in CLL.

Autosomal dominant TUBB3-related syndrome: Fetal, radiologic, clinical and morphological features.

Objective: To describe fetal, clinical, radiological, morphological features of TUBB3 related syndrome.

Methods: We report two families each of two generations harboring a novel and a previously described heterozygous TUBB3 pathogenic variants. We compared these patients with other published TUBB3-related cases.

Two separate functions of NME3 critical for cell survival underlie a neurodegenerative disorder.

We report a patient who presented with congenital hypotonia, hypoventilation, and cerebellar histopathological alterations. Exome analysis revealed a homozygous mutation in the initiation codon of the gene, which encodes an NDP kinase. The initiation-codon mutation leads to deficiency in NME3 protein expression.

Prenatal and postnatal presentation of PRMT7 related syndrome: Expanding the phenotypic manifestations.

Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyze the transfer of methyl groups from S-adenosyl-l-methionine to nitrogen atoms on arginine residues. Arginine methylation is involved in multiple biological processes, such as signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. Currently, 10 patients have been described with mutations in PRMT7.

LMOD3-Associated Nemaline Myopathy: Prenatal Ultrasonographic, Pathologic, and Molecular Findings.

To describe the prenatal presentation, including ultrasonographic, histologic, and molecular findings, in 2 fetuses affected with LMOD3-related nemaline myopathy. Prenatal ultrasonographic examinations and histopathologic studies were performed on 2 fetuses with evidence of nemaline myopathy. To establish a molecular diagnosis, whole-exome sequencing was pursued for the affected fetuses.

Unique Imaging Features Enabling the Prenatal Diagnosis of Developmental Venous Anomalies: A Persistent Echogenic Brain Lesion Drained by a Collecting Vein in Contrast with Normal Brain Parenchyma on MRI.

Objective: To describe the prenatal imaging features enabling diagnosis of developmental venous anomalies (DVA).

Methods: Four fetuses with unexplained persistent echogenic parenchymal brain lesions were studied. The evaluation included dedicated neurosonography, fetal MRI, serology for intrauterine infection, screening for coagulation abnormalities, and chromosomal microarray.

Characteristics of orbital lymphoma: a clinicopathological study of 26 cases.

Objective: Evaluation of the medical data of patients with orbital and adnexal lymphoma.

Design: Cohort study of all cases diagnosed with orbital or adnexal lymphoma at Meir Medical Center between 1993 and 2007.

Participants: Twenty-six patients, with intraorbital or subconjunctival masses with orbital involvement, were examined and followed up between 1 and 8 years.

Familial Brain Periventricular Pseudocysts.

Introduction: We report the rare finding of recurrent periventricular pseudocysts (PVPC) in consecutive pregnancies in 4 families and their postnatal outcome.

Materials And Methods: We reviewed the databases of 3 large ultrasound units searching for the diagnosis of PVPC in 2 pregnancies of the same patient.

Results: The first case of recurrent PVPC was diagnosed in 2011 and since then 3 additional families were diagnosed (8 cases of PVPC all in all).

Telomere homeostasis in trophoblasts and in cord blood cells from pregnancies complicated with preeclampsia.

Background: Telomeres are nucleoprotein structures, essential for chromosome stability and cell survival. Telomeres are progressively shortened with each cell division and by environmental factors. Telomere loss has been linked to age and stress-induced premature senescence.

Safety and efficacy of intrastromal injection of 5% natamycin in experimental fusarium keratitis.

Purpose: To compare the efficacy of combined intrastromal injection and topical natamycin 5% to standard topical therapy alone in an experimental rabbit model of Fusarium keratitis.

Methods: Fungal keratitis was induced in the right eyes of 12 New Zealand rabbits by stromal injection of Fusarium solani spore suspension into the cornea. Four days after inoculation, animals were randomly assigned to 2 different treatment groups (n=6 in each group).

Waterhouse Friderichsen syndrome complicating fulminant Enterobacter cloacae sepsis in a preterm infant: the unresolved issue of corticosteroids.

Bilateral adrenal hemorrhage can complicate severe sepsis in the neonate and is most commonly attributed to meningococcal disease; however, it can be caused by other etiologic agents as well. We report herein a fatal case of Enterobacter cloacae sepsis in a preterm infant, resulting in massive adrenal hemorrhages. This is the first documented case of adrenal hemorrhage following infection with this pathogen.

T cell-derived microvesicles induce mast cell production of IL-24: relevance to inflammatory skin diseases.

Background: It has recently been shown that microvesicles derived from activated T cells can stimulate human mast cells (MCs) to degranulate and release several cytokines.

Objective: The aim of this study was to characterize microvesicle-induced MC expression patterns. Through identification of unique cytokine and chemokine expression, we attempted to reveal pathogenetic roles for this pathway of MC activation.

Senescence in amniocytes and placentas from trisomy 21 pregnancies.

Objective: Senescence has been described as a stable cell proliferation arrest resulting from the progression of primary human fibroblasts through a finite number of population doublings in vitro. Accelerated telomere shortening was observed in pregnancies complicated by intrauterine growth restriction, in placentas of diabetic mothers and trisomy 21 amniocytes. We hypothesized that under conditions of stress, telomeres in placentas will be shorter and there will be more cells with the senescence phenotype.

p53 Regulates insulin-like growth factor-I receptor gene expression in uterine serous carcinoma and predicts responsiveness to an insulin-like growth factor-I receptor-directed targeted therapy.

The role of the insulin-like growth factors (IGF) in endometrial cancer has been well established. The IGF-I receptor (IGF-IR), which mediates the biological actions of IGF-I, is usually overexpressed in endometrial tumours. Uterine serous carcinoma (USC) constitutes a defined histological category among endometrial cancers.

CO2 laser-assisted sclerectomy surgery part I: concept and experimental models.

Purpose: To evaluate the safety and performance of a second-generation device for CO2 laser-assisted sclerectomy surgery system in experimental models.

Materials And Methods: Laser-assisted deep sclerectomy using a modified CO2 laser system (OT-134-"IOPtiMate"; IOPtima Ltd, Israel) was performed in 3 experimental models: enucleated pig eyes, human cadaver eyes, and live rabbit eyes. A half-thickness scleral flap was created, and a CO2 laser with a beam-manipulating system was used to achieve deep scleral ablation over the Schlemm canal zone.

Does normal fetal brain ultrasound predict normal neurodevelopmental outcome in congenital cytomegalovirus infection?

Objective: We evaluated the neuropsychological outcome of children with proven congenital cytomegalovirus (CMV) infection and normal consecutive fetal neurosonographic examinations.

Methods: We retrospectively reviewed laboratory and imaging findings of children with congenital CMV infection. The study group consisted of children with a positive polymerase chain reaction (PCR) in amniotic fluid and virus isolation in urine in the first week of life, and normal fetal ultrasonographic (US) examination findings, including a normal multiplanar neurosonographic evaluation.

BRCA1/2 germline mutations in Jewish patients with uterine serous carcinoma.

Introduction: Whether and to what extent germline mutations in the BRCA1 and BRCA2 genes increase the risk for developing uterine serous carcinoma (USC) remain controversial. We assessed the rate of the 3 predominant BRCA1/2 mutations in Jewish patients with USC and the relevance of carrier status to clinicopathological features and survival.

Methods: Jewish patients with histologically confirmed USC diagnosed between April 1997 and December 2007 were genotyped for the 3 predominant BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations.

TERC telomerase subunit gene copy number in placentas from pregnancies complicated with intrauterine growth restriction.

Introduction: intrauterine growth restriction (IUGR) is a significant cause of both short- and long-term morbidity and mortality. IUGR secondary to placental dysfunction is correlated with telomere shortening. Telomerase is an enzyme complex that elongates telomeres.

A large homozygous deletion in the SAMHD1 gene causes atypical Aicardi-Goutiéres syndrome associated with mtDNA deletions.

Aicardi-Goutiéres syndrome (AGS) is a genetic neurodegenerative disorder with clinical symptoms mimicking a congenital viral infection. Five causative genes have been described: three prime repair exonuclease1 (TREX1), ribonucleases H2A, B and C, and most recently SAM domain and HD domain 1 (SAMHD1). We performed a detailed clinical and molecular characterization of a family with autosomal recessive neurodegenerative disorder showing white matter destruction and calcifications, presenting in utero and associated with multiple mtDNA deletions.

Telomeres are shorter in placental trophoblasts of pregnancies complicated with intrauterine growth restriction (IUGR).

Objective: Telomeres are nucleoprotein structures located at the termini of chromosomes, and protect them from fusion and degradation. Telomeres are progressively shortened with each mitotic cycle and by environmental factors. We hypothesized that antepartum stress can lead to accelerated telomere shortening in placental trophoblasts, and plays a role in intrauterine growth restriction (IUGR).

Short telomeres may play a role in placental dysfunction in preeclampsia and intrauterine growth restriction.

Objective: Telomeres shorten and aggregate with cellular senescence and oxidative stress. Telomerase and its catalytic component human telomerase reverse-transcriptase regulate telomere length. The pathogenesis of preeclampsia and intrauterine growth restriction involves hypoxic stress.