Neuroinflammation, mitochondrial defects and neurodegeneration in mucopolysaccharidosis III type C mouse model.

Severe progressive neurological paediatric disease mucopolysaccharidosis III type C is caused by mutations in the HGSNAT gene leading to deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase involved in the lysosomal catabolism of heparan sulphate. To understand the pathophysiology of the disease we generated a mouse model of mucopolysaccharidosis III type C by germline inactivation of the Hgsnat gene. At 6-8 months mice showed hyperactivity, and reduced anxiety.

Glycogen Storage Disease Type IV and Early Implantation Defect: Early Trophoblastic Involvement Associated with a New GBE1 Mutation.

A 29-year-old primigravida presented with a spontaneous miscarriage at 8 weeks of gestation. There was no consanguinity in the family. Aspiration was performed.

Clinical and electrophysiological features in a French family presenting with seipinopathy.

Seipinopathies are a group of inherited diseases affecting upper and lower motor neurons due to mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2). We report a French family carrying the N88S mutation in the BSCL2 gene. A 12-yr-old girl complained of bilateral asymmetrical pes cavus with right hand motor deficit and amyotrophy, asymmetrical leg amyotrophy and pyramidal signs.

Inverse relationship between hSHBG affinity for testosterone and hSHBG concentration revealed by surface plasmon resonance.

A wide range of human sex hormone-binding globulin (hSHBG) affinity constants for testosterone (KA_hSHBG) has been reported in literature. To bring new insight on the KA_hSHBG value, we implemented a study of the molecular interactions occurring between testosterone and its plasma transport proteins by using surface plasmon resonance. The immobilization on the sensorchip of a testosterone derivative was performed by an oligoethylene glycol linker.

[Neonatal enterovirus infections reported in France in 2012].

Enteroviruses (EVs) are among the most common viruses infecting humans. One-third of EV infections affect children under 1 year of age. Neonatal EV infections lead to a wide range of clinical manifestations, from mild febrile illness to severe, potentially fatal sepsis-like conditions with multiorgan failure.

Data from a large European study indicate that the outcome of primary hyperoxaluria type 1 correlates with the AGXT mutation type.

Primary hyperoxaluria type 1 displays a heterogeneous phenotype, likely to be affected by genetic and non-genetic factors, including timeliness of diagnosis and quality of care. As previous genotype-phenotype studies were hampered by limited patient numbers the European OxalEurope Consortium was constituted. This preliminary retrospective report is based on 526 patients of which 410 have the AGXT genotype defined.

Charcot-Marie-Tooth disease type 2A: from typical to rare phenotypic and genotypic features.

Importance: Axonal Charcot-Marie-Tooth disease (CMT) is genetically heterogeneous, with 11 genes identified. Axonal CMT has most frequently been associated with mutations in the MFN2 gene (CMT2A).

Objectives: To describe the clinical and molecular features of CMT2A, to delineate prognostic factors, to understand connections between a certain phenotype and more serious clinical consequences, and to identify interactions among the associated genes.

Peripheral myelin protein 22 gene duplication with atypical presentations: a new example of the wide spectrum of Charcot-Marie-Tooth 1A disease.

Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are both autosomal-dominant disorders linked to peripheral myelin anomalies. CMT1A is associated with a Peripheral Myelin Protein 22 (PMP22) duplication, whereas HNPP is due to a PMP22 deletion on chromosome 17. In spite of this crucial difference, we report three observations of patients with the 1.

Validation of a microbead-based format for spoligotyping of Legionella pneumophila.

A 42-plex clustered regularly interspaced short palindromic repeat (CRISPR)-based typing technique (spoligotyping) was recently developed at the French National Reference Center for Legionella. It allows the subtyping of the Legionella pneumophila sequence type 1/Paris pulsotype. In this report, we present the transfer of the membrane-based spoligotyping technique to a microbead-based multiplexed format.

The variant hERG/R148W associated with LQTS is a mutation that reduces current density on co-expression with the WT.

Background: A variant of the ether-à-go-go related channel (hERG), p.Arg148Trp (R148W) was found at heterozygous state in two infants who died from sudden infant death syndrome (SIDS), one with documented prolonged QTc and Torsade de Pointes (TdP), and in an adult woman with QTc >500 ms, atrioventricular block and TdP. This variant was previously reported in cases of severe ventricular arrhythmia but very rarely in control subjects.

Severe axial myopathy in McArdle disease.

Importance: McArdle disease is a nonlysosomal glycogenosis that classically manifests with exercise-induced pain from childhood. Fixed weakness may occur from the fifth decade and is typically mild and located around the shoulder girdle.

Observations: We describe a 61-year-old man with exercise-induced pain from a young age and a 3-year history of weight loss and an elevated creatine kinase level up to 4000 U/L.

Identification of legionella in clinical samples.

Currently, several methods are used for the detection of Legionella in clinical samples, and these methods constitute part of the criteria for defining legionellosis cases. Urinary antigen detection is the first-line diagnostic test, although this test is limited to L. pneumophila serogroup 1 (Lp1) (Helbig et al.

[Bronchiolo-alveolar carcinoma and lung transplantation].

Introduction: Bronchiolo-alveolar carcinoma is a controversial indication for lung transplantation because of the risk of recurrence. We report three cases and propose some risk factors for recurrence.

Case Reports: Our study concerns three patients transplanted at the Louis-Pradel Hospital between 1991 and 2010.

[Contribution of genotyping in Fabry's disease].

Fabry's disease is an X-linked disorder due to mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A. Clinically, most patients present with the "classical" form, though "variant" forms with inaugural or preminent heart or kidney involvement have been described. Heterozygous women are most often symptomatic though generally less severely affected than men.

[Contribution of the measurement of globotriaosylceramide in urine to the diagnosis and follow-up of Fabry disease].

Globotriaosylceramide (Gb(3)) has been measured in urine of 35 male hemizygotes and 66 female heterozygotes for Fabry disease (FD). In males, Gb(3) measurement allows to confirm the diagnosis which is based on deficient α-galactosidase A (α-Gal A) activity in leukocytes. Our results show that hemizygotes for classic FD have increased Gb(3) and C24/C18 isoforms ratio.

Amino acid profiling for the diagnosis of inborn errors of metabolism.

The diagnosis of inherited metabolic disorders of amino acid (AA) metabolism is based on the qualitative and/or the quantitative analysis of AAs, mainly in blood and urine. For years, the most widespread technique in use was ion-exchange chromatography followed by post-column derivatization with ninhydrin, a method which is the basis of numerous automated AA analyzers with a throughput of about eight samples/day. The emergence of tandem mass spectrometry (MS/MS) coupled to liquid chromatography (LC) has made possible the measurement of many metabolites for the diagnosis of inborn errors of metabolism.

[Auguste Lumière (1862-1943). Cinematography...and microbiology].

Auguste Lumière was the most inventive of the two brothers in the area of therapeutics and pharmacology. In 1896 he created his laboratory of experimental physiology where he discovered some organo-metallic derivatives active against syphilis, the oral vaccination against typhoid, vaseline gauze against burns. Unselfish amateur or real scientist he was a self-taught man who expended a lot of industrial activity even on erroneous scientific bases as he publicly refused the phenomenon of tuberculosis contagion in 1930.

A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is the most common cause of inherited peripheral neuropathy, with an estimated frequency of 1/2500. We studied a large family with 17 patients affected by the axonal form of CMT (CMT2). Analysis of the 15 genes or loci known to date was negative.

Development and implementation of a novel assay for L-2-hydroxyglutarate dehydrogenase (L-2-HGDH) in cell lysates: L-2-HGDH deficiency in 15 patients with L-2-hydroxyglutaric aciduria.

L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by mutations in the gene encoding L-2-hydroxyglutarate dehydrogenase. An assay to evaluate L-2-hydroxyglutarate dehydrogenase (L-2-HGDH) activity in fibroblast, lymphoblast and/or lymphocyte lysates has hitherto been unavailable. We developed an L-2-HGDH enzyme assay in cell lysates based on the conversion of stable-isotope-labelled L-2-hydroxyglutarate to 2-ketoglutarate, which is converted into L-glutamate in situ.