Genetic testing in focal segmental glomerulosclerosis: in whom and when?

Background: Genetic causes are increasingly recognized in patients with focal segmental glomerulosclerosis (FSGS), but it remains unclear which patients should undergo genetic study. Our objective was to determine the frequency and distribution of genetic variants in steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) and in FSGS of undetermined cause (FSGS-UC).

Methods: We performed targeted exome sequencing of 84 genes associated with glomerulopathy in patients with adult-onset SRNS-FSGS or FSGS-UC after ruling out secondary causes.

Genetic Kidney Diseases (GKDs) Modeling Using Genome Editing Technologies.

Genetic kidney diseases (GKDs) are a group of rare diseases, affecting approximately about 60 to 80 per 100,000 individuals, for which there is currently no treatment that can cure them (in many cases). GKDs usually leads to early-onset chronic kidney disease, which results in patients having to undergo dialysis or kidney transplant. Here, we briefly describe genetic causes and phenotypic effects of six GKDs representative of different ranges of prevalence and renal involvement (ciliopathy, glomerulopathy, and tubulopathy).

Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians.

Gitelman and Bartter syndromes are rare inherited diseases that belong to the category of renal tubulopathies. The genes associated with these pathologies encode electrolyte transport proteins located in the nephron, particularly in the Distal Convoluted Tubule and Ascending Loop of Henle. Therefore, both syndromes are characterized by alterations in the secretion and reabsorption processes that occur in these regions.

De novo mutations identified by exome sequencing implicate rare missense variants in SLC6A1 in schizophrenia.

Schizophrenia is a highly polygenic disorder with important contributions from both common and rare risk alleles. We analyzed exome sequencing data for de novo variants (DNVs) in a new sample of 613 schizophrenia trios and combined this with published data to give a total of 3,444 trios. In this new data, loss-of-function (LoF) DNVs were significantly enriched among 3,471 LoF-intolerant genes, which supports previous findings.

Publisher Correction: Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Targeted Sequencing of 10,198 Samples Confirms Abnormalities in Neuronal Activity and Implicates Voltage-Gated Sodium Channels in Schizophrenia Pathogenesis.

Background: Sequencing studies have pointed to the involvement in schizophrenia of rare coding variants in neuronally expressed genes, including activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes; however, larger samples are required to reveal novel genes and specific biological mechanisms.

Methods: We sequenced 187 genes, selected for prior evidence of association with schizophrenia, in a new dataset of 5207 cases and 4991 controls. Included among these genes were members of ARC and NMDAR postsynaptic protein complexes, as well as voltage-gated sodium and calcium channels.

Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total.

Identification of putative second genetic hits in schizophrenia carriers of high-risk copy number variants and resequencing in additional samples.

Copy number variants (CNVs) conferring risk of schizophrenia present incomplete penetrance, suggesting the existence of second genetic hits. Identification of second hits may help to find genes with rare variants of susceptibility to schizophrenia. The aim of this work was to search for second hits of moderate/high risk in schizophrenia carriers of risk CNVs and resequencing of the relevant genes in additional samples.

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls.

Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.

Common single-nucleotide polymorphisms (SNPs) account for a large proportion of the heritability of obsessive-compulsive disorder (OCD). Co-ocurrence of OCD and schizophrenia is commoner than expected based on their respective prevalences, complicating the clinical management of patients. This study addresses two main objectives: to identify particular genes associated with OCD by SNP-based and gene-based tests; and to test the existence of a polygenic risk shared with schizophrenia.

Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia.

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband-parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing.

An efficient screening method for simultaneous detection of recurrent copy number variants associated with psychiatric disorders.

Several recurrent copy number variants (CNVs) increasing risk to neuropsychiatric diseases have been identified in recent years. They show variable clinical expressivity, being associated with different disorders, and incomplete penetrance. However, due to its very low frequency, the full variety of clinical outcomes associated with each one of these CNVs is unknown.

De novo mutations in schizophrenia implicate synaptic networks.

Inherited alleles account for most of the genetic risk for schizophrenia. However, new (de novo) mutations, in the form of large chromosomal copy number changes, occur in a small fraction of cases and disproportionally disrupt genes encoding postsynaptic proteins. Here we show that small de novo mutations, affecting one or a few nucleotides, are overrepresented among glutamatergic postsynaptic proteins comprising activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-d-aspartate receptor (NMDAR) complexes.

Role of DISC1 interacting proteins in schizophrenia risk from genome-wide analysis of missense SNPs.

A balanced translocation affecting DISC1 cosegregates with several psychiatric disorders, including schizophrenia, in a Scottish family. DISC1 is a hub protein of a network of protein-protein interactions involved in multiple developmental pathways within the brain. Gene set-based analysis has been proposed as an alternative to individual analysis of single nucleotide polymorphisms (SNPs) to get information from genome-wide association studies.

[Subcutaneously inserted central intravascular devices in the pediatric oncology patient: can we minimize their infection].

Long-term indwelling central venous access devices are frequently used in pediatric patients. Their main complication is infection, that can even mean their removal. We try to identify the risk factors really involved in this complication and in their removal.

[Cold-knife retrograde endoscopic endopyelotomy (Cutting-Balloon) in children with ureteropelvic junction obstruction: early results].

Background: To present our early experience in the use of Cutting-Balloon for the treatment of resistant or relapsed ureteropelvic junction obstruction (UPJO) after a prior endourological retrograde high-pressure balloon dilatation (RHPBD).

Materials And Methods: Patients with progressive hydronephrosis and impaired drainage of the renal pelvis on a diuretic renal scan were treated with RHPBD. In those patients with resistant UPJO (waist persistence after dilatation) or relapsed UPJO, we consider using a Cutting-Balloon as an alternative to our current protocol (second RHPBD or open surgery).

[Response to treatment with corticoids in a case of inflammatory amyloid angiopathy without performing a biopsy].

Introduction: Inflammatory amyloid angiopathy (IAA) is an infrequent presenting symptom of the recently recognised cerebral amyloid angiopathy and its definitive diagnosis is reached by means of pathological analyses.

Aim: We report the case of a male patient with IAA and good clinical, neuropsychological and neuroimaging response to treatment with corticoids; a biopsy of brain tissue was not considered necessary.

Case Report: The patient, 68 years old and diagnosed with Alzheimer's disease, suffered from generalised seizures followed by a language disorder and hemiparesis of the right-hand side.

[Role of peritoneal drainage in necrotizing enterocolitis in critical infants with extremely low birth weight].

Introduction: Peritoneal drainage is one of the options for treatment in necrotizing enterocolitis (NEC). Currently its role is controversial as an alternative to laparotomy in low birthweight and mortality associated with both procedures is high (35-55%).

Material And Methods: We reviewed 30 low-weight premature (< 1000 g) with NEC treated surgically.

Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia.

Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs).

Methods: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results.

[Hypertrophic pyloric stenosis: comparison between transversal and supraumbilical incision].

Background/purpose: The treatment of hypertrophic pyloric stenosis is the Fredet-Ramstedt pyloromyotomy. It is controversial what surgical approach to choose. We evaluate our outcome with the right upper quadrant (RUQ) and the supraumbilical (SU) approach.

[Phimosis: dorsal slit or circumcision?].

Introduction: Phimosis is perhaps one of the most frequent consultation on pediatric surgery clinics throught the world. The aim of this study is to compare the two procedures more frequently performed in our hospital: dorsal slit and circumcision. PATIENTS Y METHODS: Retrospective study of 1698 patients who were admitted for elective surgical treatment of phimosis between 2003 and 2009.

Syntheses and structures of thermally stable diketiminato complexes of gold and copper.

While most metallic elements across the Periodic Table form stable chelating β-diketiminato complexes, examples of Au(I) are conspicuous by their absence. We report here the reaction of K[HC(F(3)CC=NR)(2)] with AuCl(PPh(3)) which provides a rare example of a thermally stable gold(I) diketiminato complex, (Ph(3)P)Au[RN=C(CF(3))CH(CF(3))C=NR] [R = 3,5-C(6)H(3)(CF(3))(2)]. The complex is highly fluxional in solution but in the solid state adopts a U-conformation.

[Percutaneous gastrostomy: when should antireflux surgery be associated?].

Introduction: Percutaneus gastrostomy placement is a procedure widely performed in children with failure to thrive or intolerance to oral feeding. At the moment of making the indication, the need of an antir-reflux surgery in the same procedure comes to question. The aim of this study was to analyse which preoperative factors are associated with a higher risk of a posterior fundoplication.