Disease relevance of SEPN1

• On the basis of clinical and morphological data, we suspected a relationship between classical MmD and the selenoprotein N gene (SEPN1), which is located on chromosome 1p36 (RSMD1 locus) and is responsible for the congenital muscular dystrophy with rigid spine syndrome (RSMD) [1].
• Rigid spine muscular dystrophy and the classical form of multiminicore disease are caused by mutations in SEPN1 gene, leading to a new clinical entity referred to as SEPN1-related myopathy [2].
• Rigid spine muscular dystrophy due to SEPN1 mutation presenting as cor pulmonale [3].
• MmD is clinically heterogeneous and distinct phenotypes have been associated with recessive mutations in either the selenoprotein N (SEPN1) or the skeletal muscle ryanodine receptor (RYR1) gene, also implicated in central core disease and malignant hyperthermia [4].
• Recent approvals for the use of gatifloxacin in the treatment of CAP due to multidrug-resistant Streptococcus pneumoniae (MDRSP) and in uncomplicated skin and skin structure infections extend the role of this drug in the treatment of bacterial infections in the US [5].

Psychiatry related information on SEPN1

• Performance on psychometric tests (Mini-Mental State Examination, Alzheimer's Disease Assessment Scale (cognition subscale), Mattis Dementia Rating Scale (initiation/perseverence subscale; MDRS I/P)) of patients of different CDR gradings was compared with that of 42 healthy controls [6].
• METHODS: Concurrent validity was evaluated using Wisconsin Card Sorting Tst (WCST) and Mattis Dementia Rating Scale-Initiation/Perseveration Subset (MDRS I/P) among 41 controls and 30 stroke patients with small subcortical infarct [7].

High impact information on SEPN1

• Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome [8].
• Analysis of three deltoid biopsy specimens from patients with typical RSMD revealed a wide myopathological variability, ranging from a dystrophic to a congenital myopathy pattern [1].
• The present study represents the first identification of a gene responsible for classical MmD, demonstrates its genetic heterogeneity, and reassesses the nosological boundaries between MmD and RSMD [1].
• A genomewide screening, followed by the analysis of 1p36 microsatellite markers in 27 informative families with MmD, demonstrated linkage to RSMD1 in eight families [1].
• Subcellular fractionation experiments and endoglycosidase H sensitivity indicate that SEPN1 is a glycoprotein-localized within the endoplasmic reticulum [2].

Chemical compound and disease context of SEPN1

• This pooled analysis of six prospective, multicentre trials aimed to determine the efficacy of moxifloxacin in community-acquired pneumonia (CAP) due to penicillin-, macrolide- and multidrug-resistant Streptococcus pneumoniae (MDRSP) [9].

Biological context of SEPN1

• Its high expression in cultured myoblasts is also down-regulated in differentiating myotubes, suggesting a role for SEPN1 in early development and in cell proliferation or regeneration [2].
• A single homozygous point mutation in a 3'untranslated region motif of selenoprotein N mRNA causes SEPN1-related myopathy [10].
• SEPN1 mutation analysis revealed that the patient was a compound heterozygote: a previously described insertion (713-714 insA), and a novel nonsense mutation (R439stop) [11].
• In the present review we discuss the most recent findings on the functional effect of mutations in SEPN1 and RYR1 and discuss how they may adversely affect muscle function and lead to the clinical phenotype [12].
• Genetic heterogeneity is recognized and up to now mutations in the genes of RYR1 and SEPN1 have been detected [13].

Anatomical context of SEPN1

• SEPN1 is present at a high level in several human fetal tissues and at a lower level in adult ones, including skeletal muscle [2].

Other interactions of SEPN1

• We report two children in whom prominent weakness of neck extensor muscles is associated with mutations in lamin A/C (LMNA) and selenoprotein N1 (SEPN1) genes, respectively [14].
• Mutations of selenoprotein N, 1 gene (SEPN1) cause rigid spine with muscular dystrophy type 1 (RSMD1), multiminicore disease, and desmin-related myopathy [15].
• In this family, linkage to the chromosome 1p rigid spine syndrome locus (RSMD1) is supported by maximum LOD scores for several markers of 1.81 at theta = 0, representing the maximum statistical power possible for this family [16].

Analytical, diagnostic and therapeutic context of SEPN1

• Here we present comparative sequence analysis and experimental data supporting the presence of a second stop codon redefinition element located adjacent to a selenocysteine-encoding UGA codon in the eukaryal gene, SEPN1 [17].
• The prevalence of nasopharyngeal carriage of the MDRSP outbreak strain was 7.8% among residents who had AIDS and 14.6% among residents with tracheostomies [18].
• OBJECTIVE: We describe an effort to reduce transmission of a multidrug-resistant Streptococcus pneumoniae (MDRSP) in a long-term-care facility (LTCF) [18].
• Long-term control of future MDRSP outbreaks should rely primarily on vaccination and strict infection control measures [19].
• RESULTS: Before the intervention, nasopharyngeal carriage of the MDRSP outbreak strain was detected in residents with AIDS and residents with tracheostomies who were not dependent on mechanical ventilation [18].

References