Introduction:Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues.Anti-U1RNP myositis is a newly described entity characte...Introduction:Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues.Anti-U1RNP myositis is a newly described entity characterized by myositis,arthritis,interstitial lung disease,and Raynaud phenomenon.We present a case of a unique combination of deep morphea in a patient with anti-U1RNP myositis.Case presentation:A 64-year-old male with 5-year history of proximal muscle weakness,polyarthritis,Raynaud phenomenon,and dyspnea on multiple immunosuppressives presented with localized infiltrated,tight,and hyperpigmented plaques over the posterior thighs and mid-to-lower back developing over the last 2 years and limiting his movement.Autoimmune workup revealed a positive ANA,anti-U1RNP antibody,anti-Jo1 antibody,and anti-Ro52 antibody.Further workup showed restrictive lung disease,kidney disease,and arthritis.Patient was diagnosed with anti-U1RNP myositis.Skin biopsy of the back lesion showed deep morphea.Discussion:Association of deep morphea with anti-U1RNP myositis is not described prior in the literature.Treatment of morphea is challenging since the patient is already on immunosuppressive medications.The patient failed methotrexate prior and is currently on Mycophenolate mofetil and Deflazacort which are reported as potential treatment for morphea.Therefore,physical therapy plus topical Tacrolimus were suggested as an initial measure to preserve the range of motion of his posterior thighs and back.This is a case of progressive deep morphea developing in a patient with a unique autoimmune profile on immunosuppressive drugs.Conclusion:Anti-U1RNP myositis is a challenging diagnosis and should be always thought of in patients with positive anti-U1RNP,myositis,interstitial lung disease,arthritis,kidney disease,and Raynaud phenomenon.Moreover,deep morphea treatment in immunosuppressed patients is challenging and different measures should be considered.展开更多
Emerging evidence suggests that intron-detaining transcripts(IDTs)are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress.However,the underly...Emerging evidence suggests that intron-detaining transcripts(IDTs)are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress.However,the underlying mechanisms of detained intron(DI)splicing are still largely unknown.Here,we suggest that post-transcriptional DI splicing is paused at the Bact state,an active spliceosome but not catalytically primed,which depends on Smad Nuclear Interacting Protein 1(SNIP1)and RNPS1(a serine-rich RNA binding protein)interaction.RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing.Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA,a basal spliceosomal component.Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration.Therefore,we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing,and that its misregulation contributes to neurodegeneration.展开更多
文摘Introduction:Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous tissues.Anti-U1RNP myositis is a newly described entity characterized by myositis,arthritis,interstitial lung disease,and Raynaud phenomenon.We present a case of a unique combination of deep morphea in a patient with anti-U1RNP myositis.Case presentation:A 64-year-old male with 5-year history of proximal muscle weakness,polyarthritis,Raynaud phenomenon,and dyspnea on multiple immunosuppressives presented with localized infiltrated,tight,and hyperpigmented plaques over the posterior thighs and mid-to-lower back developing over the last 2 years and limiting his movement.Autoimmune workup revealed a positive ANA,anti-U1RNP antibody,anti-Jo1 antibody,and anti-Ro52 antibody.Further workup showed restrictive lung disease,kidney disease,and arthritis.Patient was diagnosed with anti-U1RNP myositis.Skin biopsy of the back lesion showed deep morphea.Discussion:Association of deep morphea with anti-U1RNP myositis is not described prior in the literature.Treatment of morphea is challenging since the patient is already on immunosuppressive medications.The patient failed methotrexate prior and is currently on Mycophenolate mofetil and Deflazacort which are reported as potential treatment for morphea.Therefore,physical therapy plus topical Tacrolimus were suggested as an initial measure to preserve the range of motion of his posterior thighs and back.This is a case of progressive deep morphea developing in a patient with a unique autoimmune profile on immunosuppressive drugs.Conclusion:Anti-U1RNP myositis is a challenging diagnosis and should be always thought of in patients with positive anti-U1RNP,myositis,interstitial lung disease,arthritis,kidney disease,and Raynaud phenomenon.Moreover,deep morphea treatment in immunosuppressed patients is challenging and different measures should be considered.
基金the Tsinghua-Peking Joint Center for Life Sciences,the Thousand-Talent Young Investigator Program,the IDG/McGovern Institute for Brain Research,the National Natural Science Foundation of China(81371361,92049114,31571097,82101495)The Beijing Municipal Science&Technology Commission(Z181100001518001,Z161100000216154)+1 种基金National Key R&D Program(2017YFC0110205)the Institute for Guo Qiang,Tsinghua University。
文摘Emerging evidence suggests that intron-detaining transcripts(IDTs)are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress.However,the underlying mechanisms of detained intron(DI)splicing are still largely unknown.Here,we suggest that post-transcriptional DI splicing is paused at the Bact state,an active spliceosome but not catalytically primed,which depends on Smad Nuclear Interacting Protein 1(SNIP1)and RNPS1(a serine-rich RNA binding protein)interaction.RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing.Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA,a basal spliceosomal component.Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration.Therefore,we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing,and that its misregulation contributes to neurodegeneration.
