Metachromatic Leukodystrophy in Morocco: Identification of Causative Variants by Next-Generation Sequencing (NGS).

(1) Background: Most rare disease patients endure long delays in obtaining a correct diagnosis, the so-called "diagnostic odyssey", due to a combination of the rarity of their disorder and the lack of awareness of rare diseases among both primary care professionals and specialists. Next-generation sequencing (NGS) techniques that target genes underlying diverse phenotypic traits or groups of diseases are helping reduce these delays; (2) Methods: We used a combination of biochemical (thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry), NGS (resequencing gene panels) and splicing assays to achieve a complete diagnosis of three patients with suspected metachromatic leukodystrophy, a neurologic lysosomal disorder; (3) Results: Affected individuals in each family were homozygotes for harmful variants in the gene, one of them novel (c.854+1dup, in family 1) and the other already described (c.

A murine model for the del(GJB6-D13S1830) deletion recapitulating the phenotype of human DFNB1 hearing impairment: generation and functional and histopathological study.

Inherited hearing impairment is a remarkably heterogeneous monogenic condition, involving hundreds of genes, most of them with very small (< 1%) epidemiological contributions. The exception is GJB2, the gene encoding connexin-26 and underlying DFNB1, which is the most frequent type of autosomal recessive non-syndromic hearing impairment (ARNSHI) in most populations (up to 40% of ARNSHI cases). DFNB1 is caused by different types of pathogenic variants in GJB2, but also by large deletions that keep the gene intact but remove an upstream regulatory element that is essential for its expression.

Novel Pathogenic Variants in the Gene Encoding Stereocilin () Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects.

Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in , encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss.

Clinical Outcomes of Patients with Chronic Neuropathic Form of Gaucher Disease in the Spanish Real-World Setting: A Retrospective Study.

This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.

Genotyping of the rs1800440 Polymorphism in CYP1B1 Gene and the rs9258883 Polymorphism in HLA-B Gene in a Spanish Cohort of 223 Patients with Frontal Fibrosing Alopecia.

The pathogenesis of frontal fibrosing alopecia has been linked to specific genetic variants. CYP1B1 codes for a component of the cytochrome p450 machinery that is involved in the metabolism of xenobiotic oestrogens. The study of the prevalence of polymorphisms in this gene may help to understand their role in the development of frontal fibrosing alopecia.

Development and validation of a sequential two-step algorithm for the screening of individuals with potential polycythaemia vera.

In 2016, the WHO included haemoglobin values within normal ranges as a diagnostic criterion for Polycythaemia Vera (PV). Since then, concerns have arisen that a large number of patients are undergoing unnecessary screening for PV. To address this issue, we estimated the prevalence of JAK2 p.

Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next-generation sequencing gene panel.

Lysosomal diseases (LD) are a group of about 70 rare hereditary disorders (combined incidence 1:5000) in which diverse lysosomal functions are impaired, impacting multiple organs and systems. The first clinical signs and symptoms are usually unspecific and shared by hundreds of other disorders. Diagnosis of LD traditionally relies on performing specific enzymatic assays, if available, upon clinical suspicion of the disorder.

DFNB1 Non-syndromic Hearing Impairment: Diversity of Mutations and Associated Phenotypes.

The inner ear is a very complex sensory organ whose development and function depend on finely balanced interactions among diverse cell types. The many different kinds of inner ear supporting cells play the essential roles of providing physical and physiological support to sensory hair cells and of maintaining cochlear homeostasis. Appropriately enough, the gene most commonly mutated among subjects with hereditary hearing impairment (HI), , encodes the connexin-26 (Cx26) gap-junction channel protein that underlies both intercellular communication among supporting cells and homeostasis of the cochlear fluids, endolymph and perilymph.

Genotypic and phenotypic characterization of methicillin-resistant Staphylococcus aureus (MRSA) clones with high-level mupirocin resistance.

A high proportion of methicillin-resistant Staphylococcus aureus isolates recovered in one year period showed high-level mupirocin-resistance (HLMUPR-MRSA) in our environment (27.2%). HLMUPR-MRSA isolates were mainly collected from skin and soft tissue samples, and diabetes was the main related comorbidity condition.

Persistence of a ST6 clone of Enterococcus faecalis genotype vanB2 in two Hospitals in Aragon (Spain).

Introduction: In order to study the evolution of the outbreak that occurred between 2009 and 2010 in 3 hospitals in Zaragoza, all vancomycin-resistant clinical Enterococcus faecalis isolates identified between 2011 and 2013 at these hospitals were characterised.

Methods: Molecular characterisation of the isolates and analysis of their clonal relationships was performed using pulsed field electrophoresis, along with a retrospective review of the patient records.

Results: A total of 79 vancomycin-resistant E.

Mutations in PRPS1 causing syndromic or nonsyndromic hearing impairment: intrafamilial phenotypic variation complicates genetic counseling.

Background: PRPS1 encodes isoform I of phosphoribosylpyrophosphate synthetase (PRS-I), a key enzyme in nucleotide biosynthesis. Different missense mutations in PRPS1 cause a variety of disorders that include PRS-I superactivity, nonsyndromic sensorineural hearing impairment, Charcot-Marie-Tooth disease, and Arts syndrome. It has been proposed that each mutation would result in a specific phenotype, depending on its effects on the structure and function of the enzyme.

Antimicrobial resistance, virulence factors and genetic lineages of hospital-onset methicillin-resistant Staphylococcus aureus isolates detected in a hospital in Zaragoza.

Introduction: MRSA population dynamics is undergoing significant changes, and for this reason it is important to know which clones are circulating in our nosocomial environment.

Materials And Methods: A total of 118 MRSA isolates were collected from clinical samples from patients with previous hospital or healthcare contact (named as hospital-onset MRSA (HO-MRSA)) during a one year period. Susceptibility testing was performed by disk diffusion and microdilution.

Contribution of mutation load to the intrafamilial genetic heterogeneity in a large cohort of Spanish retinal dystrophies families.

Purpose: The aim of this study was to deepen our knowledge on the basis of intrafamilial genetic heterogeneity of inherited retinal dystrophies (RD) to further discern the contribution of individual alleles to the pathology.

Methods: Families with intrafamilial locus and/or allelic heterogeneity were selected from a cohort of 873 characterized of 2468 unrelated RD families. Clinical examination included visual field assessments, electrophysiology, fundus examination, and audiogram.

Carbapenem-resistant Pseudomonas aeruginosa strains from a Spanish hospital: characterization of metallo-beta-lactamases, porin OprD and integrons.

Molecular typing and mechanisms of carbapenem resistance such as alterations in porin OprD and presence of metallo-beta-lactamases (MBLs), as well as integrons have been studied in a collection of carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates from a Spanish hospital. One hundred and twenty-three CRPA isolates were recovered from different samples of 80 patients. Clonal relationship among CRPA was analyzed by SpeI-PFGE.

Comparison of local features from two Spanish hospitals reveals common and specific traits at multiple levels of the molecular epidemiology of metallo-β-lactamase-producing Pseudomonas spp.

Twenty-seven well-characterized metallo-β-lactamase (MBL)-producing Pseudomonas strains from two distantly located hospitals were analyzed. The results revealed specific features defining the multilevel epidemiology of strains from each hospital in terms of species, clonality, predominance of high-risk clones, composition/diversity of integrons, and linkages of Tn402-related structures. Therefore, despite the global trends driving the epidemiology of MBL-producing Pseudomonas spp.

Characterization of plasmid-mediated β-lactamases in fecal colonizing patients in the hospital and community setting in Spain.

Aim: Active surveillance of plasmid-mediated β-lactamase-producing Enterobacteriaceae (PMBL-E) in fecal carriers in the hospital and in the community setting in a non-outbreak period of time.

Methods: Patients were screened for carriage of Enterobacteriaceae resistant to expanded-spectrum cephalosporins and PMBL-E were characterized (extended-spectrum-β-lactamase [ESBL], plasmid-mediated AmpC β-lactamase [pAmpC], and carbapenemases) by PCR and sequencing.

Results: The prevalence of ESBL and pAmpC carriers was 5.

A novel splice-site mutation in the GJB2 gene causing mild postlingual hearing impairment.

The DFNB1 subtype of autosomal recessive, nonsyndromic hearing impairment, caused by mutations affecting the GJB2 (connexin-26) [corrected] gene, is highly prevalent in most populations worldwide. DFNB1 hearing impairment is mostly severe or profound and usually appears before the acquisition of speech (prelingual onset), though a small number of hypomorphic missense mutations result in mild or moderate deafness of postlingual onset. We identified a novel GJB2 splice-site mutation, c.

Hearing is normal without connexin30.

Gjb2 and Gjb6, two contiguous genes respectively encoding the gap junction protein connexin26 (Cx26) and connexin 30 (Cx30) display overlapping expression in the inner ear. Both have been linked to the most frequent monogenic hearing impairment, the recessive isolated deafness DFNB1. Although there is robust evidence for the direct involvement of Cx26 in cochlear functions, the contribution of Cx30 is unclear since deletion of Cx30 strongly downregulates Cx26 both in human and in mouse.

Epidemiological features, resistance genes, and clones among community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) isolates detected in northern Spain.

Twenty-nine community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) isolates were prospectively selected according to epidemiological criteria among 374 MRSA isolates collected in our laboratory during 2009-2010 in order to determine which community-associated MRSA (CA-MRSA) and healthcare-associated MRSA (HA-MRSA) clones are circulating in the community in northern Spain. PVL genes were detected in 5 strains (17.2%) that belonged to SCCmec type IV or V and to the agr group I (ST8 and ST2050), agr group II (ST121), and agr group III (ST30 and ST852).

Genetics of isolated auditory neuropathies.

Auditory neuropathies are disorders combining absent or abnormal auditory brainstem responses with preserved otoacoustic emissions and/or cochlear microphonics. These features indicate a normal function of cochlear outer hair cells. Thus, the primary lesion might be located in the inner hair cells, in the auditory nerve or in the intervening synapse.

The DFNB1 subtype of autosomal recessive non-syndromic hearing impairment.

Inherited hearing impairment is a frequent and highly heterogeneous condition. Among the different subtypes of autosomal recessive non-syndromic hearing impairment, DFNB1 is remarkable for its high frequency in most populations. It is caused by mutations in the coding region or splice-sites of the GJB2 gene, or by mutations affecting regulatory sequences that are essential for the expression of this gene.

Nosocomial outbreak of methicillin- and linezolid-resistant Staphylococcus epidermidis associated with catheter-related infections in intensive care unit patients.

A total of 128 isolates associated with catheter-related infections was recovered from 101 intensive care unit patients in a Spanish hospital during March 2008 to August 2009, and 27 of these isolates (from 21 patients) were typed as methicillin- and linezolid-resistant Staphylococcus epidermidis. Thirteen of these 21 patients (62%) had received linezolid during the 3 months preceding S. epidermidis recovery.