Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization.

Background And Objectives: Genetic white matter disorders (GWMD) are of heterogeneous origin, with >100 causal genes identified to date. Classic targeted approaches achieve a molecular diagnosis in only half of all patients. We aimed to determine the clinical utility of singleton whole-exome sequencing and whole-genome sequencing (sWES-WGS) interpreted with a phenotype- and interactome-driven prioritization algorithm to diagnose GWMD while identifying novel phenotypes and candidate genes.

Early and long-term effect of the treatment with pyridostigmine in patients with GMPPB-related congenital myasthenic syndrome.

GMPPB mutations cause congenital myasthenic syndromes (CMS) overlapping with muscular dystrophy. Treatment with pyridostigmine has been reported to be effective in those patients. Nevertheless, results of functional motor assessments to determine its precise impact on the short and long term were not available.

Delineating the neurological phenotype in children with defects in the ECHS1 or HIBCH gene.

The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding and natural history studies are necessary to improve clinical management. From 42 patients with Leigh syndrome studied by massive parallel sequencing, we identified five patients with SCEH and HIBCH deficiency. Fourteen additional patients were recruited through collaborations with other centres.

Posttraumatic stress disorder in urban women.

Purpose Of Review: To provide an update of recent or relevant studies on posttraumatic stress disorder (PTSD) in urban women, with a special focus on biopsychosocial risk factors.

Recent Findings: Urbanization itself can increase the risk for PTSD due to the concentration of poverty, substance use and crime. Women are usually at a greater social and economic disadvantage and are victims of collective and domestic violence more often than men.

Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy.

Sphingolipid imbalance is the culprit in a variety of neurological diseases, some affecting the myelin sheath. We have used whole-exome sequencing in patients with undetermined leukoencephalopathies to uncover the endoplasmic reticulum lipid desaturase DEGS1 as the causative gene in 19 patients from 13 unrelated families. Shared features among the cases include severe motor arrest, early nystagmus, dystonia, spasticity, and profound failure to thrive.

Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells.

Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NCH)(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line.

Homozygous deletion of an EGR2 enhancer in congenital amyelinating neuropathy.

The transcription factor EGR2 is expressed in Schwann cells, where it controls peripheral nerve myelination. Mutations of EGR2 have been found in patients with congenital hypomyelinating neuropathy or Charcot-Marie-Tooth disease type 1D. In a patient with congenital amyelinating neuropathy, we observed pathological abnormalities recapitulating the peripheral nervous system phenotype of homozygous Egr2-null mice.

[Epilepsy in children in Navarre].

Background: To estimate the annual incidence rate of epilepsy, as well as the relative distribution of the different epilepsies and epileptic syndromes in children.

Material And Methods: All incident cases of children living in Navarre below 15 years of age with a newly diagnosed epilepsy (years 2003 through 2005) have been registered in a prospective study. Epidemiological and clinical data and complementary studies were collected.

[Psychomotor development of the child and its evaluation in primary care].

The evaluation of psychomotor development is one of the basic activities of everyday paediatric practice, since it helps us not only to determine if the child shows some alteration but also to confirm that the child is healthy. It is thus essential to be able to carry out a suitable evaluation, given that an alteration in this might be the only expression of a disorder of the nervous system. Early detection of any dysfunction contributes to a possible early treatment and to minimising the appearance of sequels.

[Clinical and neuropathological study of two brothers with Cockayne syndrome].

Introduction: Cockayne syndrome (CS) is a rare autosomal recessive disease which is characterized by physical and mental retardation, progressive neurological disfunction, photosensitivity and other cutaneous features. Usually they present ophthalmologic abnormalities as well as other heterogenous clinical, radiological and pathologic features as leucodistrophy and calcifications in central nervous system and segmental demyelination in peripheral nervous system.

Clinical Cases: Two brothers, sons of healthy unrelated parents, are presented.

Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI).

Lysinuric protein intolerance (LPI; MIM 222700) is an autosomal recessive disorder characterized by defective transport of the cationic amino acids lysine, arginine and ornithine at the basolateral membrane of the polar epithelial cells in the intestine and renal tubules, and by hyperammonemia after high-protein meals. LPI is caused by mutations in the SLC7A7 (solute carrier family 7, member 7) gene encoding y(+)LAT-1 (y(+)L amino acid transporter-1), which co-induces together with 4F2 heavy chain (4F2hc) system y(+)L in Xenopus oocytes. All Finnish LPI patients share the same founder mutation 1181-2A-->T (LPI(Fin)) not found in LPI patients elsewhere.

[Familial benign partial epilepsy of early infancy].

Introduction And Clinical Cases: We present two patients who at the ages of 5 and 17 months respectively presented with convulsive crises with motor signs, of partial onset and secondary generalization, which eventually became normal. Both patients had a family history of first degree relatives with similar illnesses and are at present-five years later-well and with normal development, school achievement and neurological examination findings. The clinical characteristics, normal biochemical and neuroimaging investigations and EEG characteristics suggest the diagnosis of benign partial epilepsy of early infancy.

[Andermann syndrome: presentation of a case].

Introduction: Peripheral neuropathy with agenesis of the corpus callosum (or Andermann's syndrome) is a hereditary autosomal recessive disorder rarely found outside certain regions of Quebec Province (Canada). It is associated with mental retardation and various dysmorphic changes. Deterioration is usually progressive with loss of motor skills, development of scoliosis during adolescence, tendency to behaviour disorders and death during the third decade (approximately).

Calcium-cadmium interaction on sugar absorption across the rabbit jejunum.

The element Cd is considered to have no biological function and is highly toxic to humans and animals. Toxic effects of this metal upon cell membrane structure and function have been shown. On the other hand, Ca is an essential element in a wide variety of cellular activities.

[Muscular phosphorylase deficiency in two siblings].

The clinical manifestation of McArdle disease rarely occur in children. A brother and a sister aged 12 and 7 years respectively are presented. Both are sons of a consanguinous marriage.

[Giant axonal neuropathy. Presentation of 2 familial cases].

A review of 20 cases of giant axonal neuropathy (4 of them familial) described in the literature, and two new cases in brothers whose parents had no consanguinity is reported. A recessive autosomic pattern of inheritance is suggested. Curly hair, a typical phenotypic feature, was not initially present in our cases.

[Myocardial infarction in relation to perinatal hypoxia].

Six newborn infants with myocardial infarction are presented. All of them had a history of perinatal hypoxemia and their natal weights were below 2,500 g. All infants developed cardiogenic "shock" during and required assisted ventilation.