RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy.

Dystrophinopathy is caused by alterations in DMD. Approximately 1% of patients remain genetically undiagnosed, because intronic variations are not detected by standard methods. Here, we combined laboratory and in silico analyses to identify disease-causing genomic variants in genetically undiagnosed patients and determine the regulatory mechanisms underlying abnormal DMD transcript generation. DMD transcripts from 20 genetically undiagnosed dystrophinopathy patients in whom no exon variants were identified, despite dystrophin deficiency on muscle biopsy, were analyzed by transcriptome sequencing. Genome sequencing captured intronic variants and their effects were interpreted using in silico tools. Targeted long-read sequencing was applied in cases with suspected structural genomic abnormalities. Abnormal DMD transcripts were detected in 19 of 20 cases; Exonization of intronic sequences in 15 cases, exon skipping in one case, aberrantly spliced and polyadenylated transcripts in two cases and transcription termination in one case. Intronic single nucleotide variants, chromosomal rearrangements and nucleotide repeat expansion were identified in DMD gene as pathogenic causes of transcript alteration. Our combined analysis approach successfully identified pathogenic events. Detection of diseasing-causing mechanisms in DMD transcripts could inform the therapeutic options for patients with dystrophinopathy.

[Anti-MOG + neuromyelitis optica spectrum disorders treated with plasmapheresis].

A 10-year-old boy developed bilateral optic neuritis and myelitis after a suspected viral infection and appendicitis. Magnetic resonance imaging (MRI) showed multiple lesions in both optic nerves, the optic chiasm, and the spinal cord. Several small lesions were also observed in the cerebellum and cerebral white matter. The serum tested negative for anti-aquaporin (AQP)-4 antibody and positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody. The diagnosis was neuromyelitis optica spectrum disorder (NMOSD). Two courses of high-dose methylprednisolone were administered; however, only a small improvement in his visual acuity was achieved. He underwent 3 courses of plasma exchange to achieve sufficient visual acuity. After the serum anti-MOG antibody titer decreased to the cut-off level, oral prednisolone and azathioprine administration were also stopped, 10 months after onset. Recently, NMO and NMOSD cases positive for anti-MOG antibodies have been reported, which showed clinical features different from those of NMO cases positive for anti-AQP4 antibody. Although most of the reported cases responded to steroid therapy, plasma exchange was required in our case. Further analysis on larger numbers of cases is needed to establish treatments for anti-MOG antibody-positive NMO and NMOSD.

Intimate partner violence among general and urban poor populations in Kathmandu, Nepal.

Comparative studies are lacking on intimate partner violence (IPV) between urban poor and general populations. The objective of this study is to identify the prevalence and risk factors of physical IPV among the general and poor populations in urban Nepal. A cross-sectional study was conducted by structured questionnaire interview. Participants included 905 ever-married women in Kathmandu aged 15 to 49 years. Of the 905 participants, 680 were randomly selected from general population and 225 were recruited from urban poor population, who lived in purposively selected two communities. The prevalence and association between ever experiencing physical IPV and sociodemographic variables were examined. Results showed that the prevalence of physical IPV was 33.8% among the urban poor population (n = 225) and 19.9% among the general population (n = 680; p < .01). Several factors were significantly associated with physical IPV in both populations: the frequency of the husband's drinking, polygyny, and lower household economic status. However, two factors were associated with physical IPV only among the general population: the husband's lower educational level and early marriage. The conclusions of this study are that compared to the general population, the urban poor population showed a significantly higher prevalence of physical IPV and differences in the associated risk factors. The urban poor population requires focused data collection as well as tailored interventions to reduce IPV.