Akshay Machanahalli Balakrishna, Bryton Perman, Mahmoud Ismayl, Dua Noor Butt, Dixitha Anugula, Ahmed Aboeata
Intravascular extension of lung adenocarcinoma is one of the four defined routes of metastasis to the heart but is rarely described in the literature. This is a rare case of primary lung adenocarcinoma with intravenous extension to the left atrium via the pulmonary vein. A 56-year-old female presented to the hospital with chest tightness and dyspnea. Chest computed tomography revealed a right hilar mass extending through the right superior pulmonary vein into the left atrium. Transthoracic echocardiography revealed a large, partially mobile left atrial mass occupying the entire atrial cavity and affecting mitral valve closure. Endobronchial ultrasound with transbronchial biopsy of the right middle lobe of the lung histologically showed a poorly differentiated adenocarcinoma compatible with the primary lung cancer. The patient was deemed a poor surgical candidate by cardiothoracic surgery due to the extent of metastasis and was started on chemoradiation. The patient's left atrial tumor mass started shrinking in size after starting the treatment. This unique case displaying intravascular extension of lung cancer to the left atrium has rarely been described in the literature.
{"title":"Atrial invasion from primary lung adenocarcinoma extension <i>via</i> the pulmonary vein.","authors":"Akshay Machanahalli Balakrishna, Bryton Perman, Mahmoud Ismayl, Dua Noor Butt, Dixitha Anugula, Ahmed Aboeata","doi":"10.5582/irdr.2022.01033","DOIUrl":"https://doi.org/10.5582/irdr.2022.01033","url":null,"abstract":"<p><p>Intravascular extension of lung adenocarcinoma is one of the four defined routes of metastasis to the heart but is rarely described in the literature. This is a rare case of primary lung adenocarcinoma with intravenous extension to the left atrium via the pulmonary vein. A 56-year-old female presented to the hospital with chest tightness and dyspnea. Chest computed tomography revealed a right hilar mass extending through the right superior pulmonary vein into the left atrium. Transthoracic echocardiography revealed a large, partially mobile left atrial mass occupying the entire atrial cavity and affecting mitral valve closure. Endobronchial ultrasound with transbronchial biopsy of the right middle lobe of the lung histologically showed a poorly differentiated adenocarcinoma compatible with the primary lung cancer. The patient was deemed a poor surgical candidate by cardiothoracic surgery due to the extent of metastasis and was started on chemoradiation. The patient's left atrial tumor mass started shrinking in size after starting the treatment. This unique case displaying intravascular extension of lung cancer to the left atrium has rarely been described in the literature.</p>","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161132/pdf/irdr-11-87.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10246479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Çağlar Fidan, Hüseyin Örün, Aslı Begüm Alper, Çiğdem Naz Ünver, Ömer Can Şahin, Zeynep Uğurlu, R. Akdur, D. Taruscio
Bloodspot screening in newborns is an exemplary public health intervention as it is essential secondary prevention with proven efficacy and benefit for the early diagnosis and prompt treatment of rare diseases. In this mini review, newborn bloodspot screening (NBS) programs of 12 countries were examined in terms of the extent of diseases/disorders screened to form recommendations for Turkey's expanded newborn screening program. Essentially, Turkey and 11 selected countries' official policies/ national programs or strategies in terms of newborn screening and the number of diseases/conditions screened were examined. The current status of spinal muscular atrophy (SMA) screening was also checked through the SMA NBS Alliance. In addition, WHO and EURORDIS guidelines for newborn screening were also reviewed. On the Pubmed database, following the search strategy "((newborn screening[Title/Abstract]) OR (newborn screening program[Title/Abstract])) OR (newborn blood spot screening[Title/Abstract])" in the PubMed database from 1 January 2008 to 1 December 2021. Diseases that will be recommended to be included in the Turkish national newborn bloodspot screening program will be presented by evaluating the updated criteria of Wilson and Jungner by constructing international comparisons. The number of diseases/disorders screened by the inspected 12 countries is eminently variable and ranges from 5 in Turkey to 51 in New York, United States of America (USA). Acknowledging the programs of other countries, it is evident that Turkey must advance its program by evaluating the epidemiological data in Turkey, the health workforce, and infrastructure while relying on the updated screening criteria. The newborn bloodspot screening program should be expanded based on the cost estimates and implemented starting with pilot applications and the diseases/disorders that are deemed appropriate should be included in the national program.
{"title":"Expanded newborn bloodspot screening: developed country examples and what can be done in Turkey.","authors":"Çağlar Fidan, Hüseyin Örün, Aslı Begüm Alper, Çiğdem Naz Ünver, Ömer Can Şahin, Zeynep Uğurlu, R. Akdur, D. Taruscio","doi":"10.5582/irdr.2022.01039","DOIUrl":"https://doi.org/10.5582/irdr.2022.01039","url":null,"abstract":"Bloodspot screening in newborns is an exemplary public health intervention as it is essential secondary prevention with proven efficacy and benefit for the early diagnosis and prompt treatment of rare diseases. In this mini review, newborn bloodspot screening (NBS) programs of 12 countries were examined in terms of the extent of diseases/disorders screened to form recommendations for Turkey's expanded newborn screening program. Essentially, Turkey and 11 selected countries' official policies/ national programs or strategies in terms of newborn screening and the number of diseases/conditions screened were examined. The current status of spinal muscular atrophy (SMA) screening was also checked through the SMA NBS Alliance. In addition, WHO and EURORDIS guidelines for newborn screening were also reviewed. On the Pubmed database, following the search strategy \"((newborn screening[Title/Abstract]) OR (newborn screening program[Title/Abstract])) OR (newborn blood spot screening[Title/Abstract])\" in the PubMed database from 1 January 2008 to 1 December 2021. Diseases that will be recommended to be included in the Turkish national newborn bloodspot screening program will be presented by evaluating the updated criteria of Wilson and Jungner by constructing international comparisons. The number of diseases/disorders screened by the inspected 12 countries is eminently variable and ranges from 5 in Turkey to 51 in New York, United States of America (USA). Acknowledging the programs of other countries, it is evident that Turkey must advance its program by evaluating the epidemiological data in Turkey, the health workforce, and infrastructure while relying on the updated screening criteria. The newborn bloodspot screening program should be expanded based on the cost estimates and implemented starting with pilot applications and the diseases/disorders that are deemed appropriate should be included in the national program.","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47463434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The human body harbors approximately 1014 cells belonging to a diverse group of microorganisms. Bacteria outnumbers protozoa, fungi and viruses inhabiting our gastrointestinal tract (GIT), commonly referred to as the "human gut microbiome". Dysbiosis occurs when the balanced relationship between the host and the gut microbiota is disrupted, altering the usual microbial population there. This increases the susceptibility of the host to pathogens, and chances of its morbidity. It is due to the fact that the gut microbiome plays an important role in human health; it influences the progression of conditions varying from colorectal cancer to GIT disorders linked with the nervous system, autoimmunity, metabolism and inheritance. A rare disease is a lethal and persistent condition affecting 2-3 people per 5,000 populaces. This review article intends to discuss such rare neurological, autoimmune, cardio-metabolic and genetic disorders of man, focusing on the fundamental mechanism that links them with their gut microbiome. Ten rare diseases, including Pediatric Crohn's disease (PCD), Lichen planus (LP), Hypophosphatasia (HPP), Discitis, Cogan's syndrome, Chancroid disease, Sennetsu fever, Acute cholecystitis (AC), Grave's disease (GD) and Tropical sprue (TS) stands to highlight as key examples, along with personalized therapeutics meant for them. This medicinal approach addresses the individual's genetic and genomic pathography, and tackles the illness with specific and effective treatments.
{"title":"Association of human gut microbiota with rare diseases: A close peep through.","authors":"Souvik Roy, Sagnik Nag, Ankita Saini, Lopamudra Choudhury","doi":"10.5582/irdr.2022.01025","DOIUrl":"https://doi.org/10.5582/irdr.2022.01025","url":null,"abstract":"<p><p>The human body harbors approximately 10<sup>14</sup> cells belonging to a diverse group of microorganisms. Bacteria outnumbers protozoa, fungi and viruses inhabiting our gastrointestinal tract (GIT), commonly referred to as the \"human gut microbiome\". Dysbiosis occurs when the balanced relationship between the host and the gut microbiota is disrupted, altering the usual microbial population there. This increases the susceptibility of the host to pathogens, and chances of its morbidity. It is due to the fact that the gut microbiome plays an important role in human health; it influences the progression of conditions varying from colorectal cancer to GIT disorders linked with the nervous system, autoimmunity, metabolism and inheritance. A rare disease is a lethal and persistent condition affecting 2-3 people per 5,000 populaces. This review article intends to discuss such rare neurological, autoimmune, cardio-metabolic and genetic disorders of man, focusing on the fundamental mechanism that links them with their gut microbiome. Ten rare diseases, including Pediatric Crohn's disease (PCD), Lichen planus (LP), Hypophosphatasia (HPP), Discitis, Cogan's syndrome, Chancroid disease, Sennetsu fever, Acute cholecystitis (AC), Grave's disease (GD) and Tropical sprue (TS) stands to highlight as key examples, along with personalized therapeutics meant for them. This medicinal approach addresses the individual's genetic and genomic pathography, and tackles the illness with specific and effective treatments.</p>","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161125/pdf/irdr-11-52.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10252755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mustafa Yakubi, D. Çiçek, Mikail Demir, Abdulbaki Yildirim, N. Hatipoğlu, Y. Ozkul, M. Dundar
Alström syndrome (AS) is a rare autosomal recessive monogenic disorder caused by mutations of the Alström syndrome 1 (ALMS1) gene, located on chromosome 2p13. It is a progressive multisystemic disease characterized mostly by obesity, sensorineural hearing loss, visual impairments, cardiomyopathy, insulin resistance and/or type 2 diabetes mellitus (T2DM), metabolic dysfunctions, non-alcoholic fatty liver disease, and chronic progressive kidney disease. Generally, the first clinical symptoms of the disease appear in the first years of life with a major variation of onset age. In this study, we aimed to examine the molecular diagnosis of a 6-year-old patient with suspected AS clinical symptoms. After applying clinical exome sequencing (CES) in the patient we found a homozygous deletion in exon 8 at the ALMS1 gene (c.2311_2312del). We identified a homozygous frameshift mutation. The reported variant was pathogenic according to the criteria of the American College of Medical Genetics and Genomics (ACMG). Thus, the patient was diagnosed with AS as a result of the combined clinical phenotype and genetic tests results. We hope the variant we found can expand the spectrum of ALMS1 variants in AS.
{"title":"Diagnosing Alström syndrome in a patient followed up with syndromic obesity for years.","authors":"Mustafa Yakubi, D. Çiçek, Mikail Demir, Abdulbaki Yildirim, N. Hatipoğlu, Y. Ozkul, M. Dundar","doi":"10.5582/irdr.2022.01024","DOIUrl":"https://doi.org/10.5582/irdr.2022.01024","url":null,"abstract":"Alström syndrome (AS) is a rare autosomal recessive monogenic disorder caused by mutations of the Alström syndrome 1 (ALMS1) gene, located on chromosome 2p13. It is a progressive multisystemic disease characterized mostly by obesity, sensorineural hearing loss, visual impairments, cardiomyopathy, insulin resistance and/or type 2 diabetes mellitus (T2DM), metabolic dysfunctions, non-alcoholic fatty liver disease, and chronic progressive kidney disease. Generally, the first clinical symptoms of the disease appear in the first years of life with a major variation of onset age. In this study, we aimed to examine the molecular diagnosis of a 6-year-old patient with suspected AS clinical symptoms. After applying clinical exome sequencing (CES) in the patient we found a homozygous deletion in exon 8 at the ALMS1 gene (c.2311_2312del). We identified a homozygous frameshift mutation. The reported variant was pathogenic according to the criteria of the American College of Medical Genetics and Genomics (ACMG). Thus, the patient was diagnosed with AS as a result of the combined clinical phenotype and genetic tests results. We hope the variant we found can expand the spectrum of ALMS1 variants in AS.","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45206702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
99mTc-sestamibi SPECT/CT is a promising nuclear medicine imaging investigation for benign renal lesions such as renal oncocytomas. The purpose of this article is to i) review the current literature on 99mTc-sestamibi SPECT/CT, ii) to review to current application of 99mTc-sestamibi SPECT/CT for indeterminate renal lesion imaging, and iii) to discuss present limitations and areas for future research. The literature has been reviewed up to April 2022 for articles relating to the application of 99mTc-sestamibi SPECT/CT for benign renal lesions including a recently published systematic review and meta-analysis performed by the authors. One study evaluating 99mTc-sestamibi SPECT alone and five studies evaluating 99mTc-sestamibi SPECT/CT have been performed to date. 99mTc-sestamibi SPECT/CT demonstrates high sensitivity and specificity for detecting benign renal lesions, particularly renal oncocytomas. 99mTc-sestamibi SPECT/CT demonstrates near-perfect specificity for benign and low-grade renal lesions. The optimal quantified threshold ratio for tumor-to-background renal parenchyma radiotracer uptake for a positive result is > 0.6. In this article, we propose a modified diagnostic algorithm for small enhancing renal masses measuring 1-4 cm in which suspected benign lesions after conventional imaging are considered for 99mTc-sestamibi SPECT-CT. In this algorithm, positive studies can be monitored with active surveillance rather than requiring invasive biopsy and/or targeted therapy.
{"title":"A review of 99mTc-sestamibi SPECT/CT for renal oncocytomas: A modified diagnostic algorithm.","authors":"M. Wilson, P. Katlariwala, J. Abele, G. Low","doi":"10.5582/irdr.2022.01027","DOIUrl":"https://doi.org/10.5582/irdr.2022.01027","url":null,"abstract":"99mTc-sestamibi SPECT/CT is a promising nuclear medicine imaging investigation for benign renal lesions such as renal oncocytomas. The purpose of this article is to i) review the current literature on 99mTc-sestamibi SPECT/CT, ii) to review to current application of 99mTc-sestamibi SPECT/CT for indeterminate renal lesion imaging, and iii) to discuss present limitations and areas for future research. The literature has been reviewed up to April 2022 for articles relating to the application of 99mTc-sestamibi SPECT/CT for benign renal lesions including a recently published systematic review and meta-analysis performed by the authors. One study evaluating 99mTc-sestamibi SPECT alone and five studies evaluating 99mTc-sestamibi SPECT/CT have been performed to date. 99mTc-sestamibi SPECT/CT demonstrates high sensitivity and specificity for detecting benign renal lesions, particularly renal oncocytomas. 99mTc-sestamibi SPECT/CT demonstrates near-perfect specificity for benign and low-grade renal lesions. The optimal quantified threshold ratio for tumor-to-background renal parenchyma radiotracer uptake for a positive result is > 0.6. In this article, we propose a modified diagnostic algorithm for small enhancing renal masses measuring 1-4 cm in which suspected benign lesions after conventional imaging are considered for 99mTc-sestamibi SPECT-CT. In this algorithm, positive studies can be monitored with active surveillance rather than requiring invasive biopsy and/or targeted therapy.","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44431230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An urgent need of therapy exists for patients with high-risk non-muscle invasive bladder cancer (NMIBC) for whom Bacillus Calmette-Guérin (BCG) refractory treatment has failed. We investigated the role of intravesical magnesium sulfate (MgSO4) therapy in the management of BCG refractory T1 high grade (G3) NMIBC. Between January 2018 and July 2021, we performed a prospective trial enrolling participants with T1 G3 NMIBC refractory in BCG therapy. All patients included were considered ineligible for or have refused to undergo radical cystectomy. Subjects are enrolled into a single treatment group of a fixed dose of intravesical MgSO4. The intravesical solution was given for 3 h bi-weekly × 6 then once per week for 12 months. Cystoscopic surveillance was performed every 3 months. Endoscopic resection was performed if suspicious findings were identified on surveillance cystoscopy to establish pathologic diagnosis. Oncological outcomes and any side effects were reported during follow-up. A total of 8 patients who received intravesical MgSO4 for refractory TG3 tumors were included in our study. The median follow-up time was 29 months (range from 23 to 36). 62.5% of the patients (5/8) achieved a complete response to intravesical MgSO4, while 25% of the patients (2/8) had a partial response and 12.5% (1/8) had persistent disease. None of the patients had disease progression. None of the patients experienced hypermagnesemia. In patients with pTG3 tumors who were refractory to BCG therapy, intravesical MgSO4 was a well-tolerated and potentially effective regimen.
{"title":"Intravesical MgSO4 for the treatment of BCG refractory T1 G3 bladder cancer: Preliminary results on efficacy and safety.","authors":"M. Moussa, M. Chakra, I. Duquesne","doi":"10.5582/irdr.2022.01057","DOIUrl":"https://doi.org/10.5582/irdr.2022.01057","url":null,"abstract":"An urgent need of therapy exists for patients with high-risk non-muscle invasive bladder cancer (NMIBC) for whom Bacillus Calmette-Guérin (BCG) refractory treatment has failed. We investigated the role of intravesical magnesium sulfate (MgSO4) therapy in the management of BCG refractory T1 high grade (G3) NMIBC. Between January 2018 and July 2021, we performed a prospective trial enrolling participants with T1 G3 NMIBC refractory in BCG therapy. All patients included were considered ineligible for or have refused to undergo radical cystectomy. Subjects are enrolled into a single treatment group of a fixed dose of intravesical MgSO4. The intravesical solution was given for 3 h bi-weekly × 6 then once per week for 12 months. Cystoscopic surveillance was performed every 3 months. Endoscopic resection was performed if suspicious findings were identified on surveillance cystoscopy to establish pathologic diagnosis. Oncological outcomes and any side effects were reported during follow-up. A total of 8 patients who received intravesical MgSO4 for refractory TG3 tumors were included in our study. The median follow-up time was 29 months (range from 23 to 36). 62.5% of the patients (5/8) achieved a complete response to intravesical MgSO4, while 25% of the patients (2/8) had a partial response and 12.5% (1/8) had persistent disease. None of the patients had disease progression. None of the patients experienced hypermagnesemia. In patients with pTG3 tumors who were refractory to BCG therapy, intravesical MgSO4 was a well-tolerated and potentially effective regimen.","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46555316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashwin Parakkaje Subramanya, J. George, M. Prabhuji, R. Bavle, Sudhakara Muniswamappa
Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease characterized by necrotising granulomatous inflammation of upper and lower respiratory tract, vasculitis and glomerulonephritis. This ailment may present with cough, haemoptysis, sinusitis, nasal deformity, skin lesions, malaise, fever, anorexia, and weight loss. Oral manifestation includes strawberry gingivitis, which is a pathognomonic clinical presentation. Here, we present a case of GPA in gingiva as the first manifestation. Clinical examination of the oral cavity revealed granular, erythematous gingival enlargement in the lower anterior teeth region involving papilla, marginal and attached gingiva with shiny and pebbled surface. Histopathological examination showed pseudoepitheliomatous hyperplasia with vasculitis and inflammation in the connective tissue, neutrophilic infiltration and abscess formation with haemorrhage were noted. Laboratory investigations revealed Proteinase 3 (PR3) antigen and Glomerular basement membrane (GBM) antigen were positive. Clinical, histopathological and laboratory investigations enabled the diagnosis of Granulomatosis with Polyangiitis. We present this rare case report of GPA with primary manifestation in gingiva.
{"title":"Granulomatosis with polyangiitis in gingiva: A rare case of isolated presentation.","authors":"Ashwin Parakkaje Subramanya, J. George, M. Prabhuji, R. Bavle, Sudhakara Muniswamappa","doi":"10.5582/irdr.2022.01045","DOIUrl":"https://doi.org/10.5582/irdr.2022.01045","url":null,"abstract":"Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease characterized by necrotising granulomatous inflammation of upper and lower respiratory tract, vasculitis and glomerulonephritis. This ailment may present with cough, haemoptysis, sinusitis, nasal deformity, skin lesions, malaise, fever, anorexia, and weight loss. Oral manifestation includes strawberry gingivitis, which is a pathognomonic clinical presentation. Here, we present a case of GPA in gingiva as the first manifestation. Clinical examination of the oral cavity revealed granular, erythematous gingival enlargement in the lower anterior teeth region involving papilla, marginal and attached gingiva with shiny and pebbled surface. Histopathological examination showed pseudoepitheliomatous hyperplasia with vasculitis and inflammation in the connective tissue, neutrophilic infiltration and abscess formation with haemorrhage were noted. Laboratory investigations revealed Proteinase 3 (PR3) antigen and Glomerular basement membrane (GBM) antigen were positive. Clinical, histopathological and laboratory investigations enabled the diagnosis of Granulomatosis with Polyangiitis. We present this rare case report of GPA with primary manifestation in gingiva.","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49210022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei-chuan Yang, Guiyang Jin, Keying Qian, Chao Zhang, W. Zhi, Dan Yang, Yan-qin Lu, Jinxiang Han
Developmental dysplasia of the hip (DDH) is a multifactorial disease, which occurs under environmental and genetic influence. The etiopathogenesis of DDH has not been fully explained. As research progresses, many candidate genes have been found to be closely related to the occurrence of DDH. In this study, we comprehensively examined 16 susceptibility genes of DDH using bioinformatics. COL1A1 encodes the pro-alpha1 chains of type I collagen, which is the major protein component of the bone extracellular matrix (ECM). The genes displaying the most statistically significant co-expression link to COL1A1 are ASPN, TGFB1, DKK1, IL-6, TENM3 and GDF5. DKK1, FRZB and WISP3 are components of the Wnt signaling pathway. CX3CR1 and GDF5 regulate chondrogenesis through the canonical Wnt signaling pathway. ASPN could induce collagen mineralization through binding with collagen and calcium. Integrated bioinformatics analysis indicates that ECM, Wnt signaling pathway and TGF-β signaling pathway are involved in the occurrence of DDH. These provide a basis for further exploring the pathogenesis of DDH.
{"title":"Comprehensive bioinformatics analysis of susceptibility genes for developmental dysplasia of the hip.","authors":"Wei-chuan Yang, Guiyang Jin, Keying Qian, Chao Zhang, W. Zhi, Dan Yang, Yan-qin Lu, Jinxiang Han","doi":"10.5582/irdr.2022.01043","DOIUrl":"https://doi.org/10.5582/irdr.2022.01043","url":null,"abstract":"Developmental dysplasia of the hip (DDH) is a multifactorial disease, which occurs under environmental and genetic influence. The etiopathogenesis of DDH has not been fully explained. As research progresses, many candidate genes have been found to be closely related to the occurrence of DDH. In this study, we comprehensively examined 16 susceptibility genes of DDH using bioinformatics. COL1A1 encodes the pro-alpha1 chains of type I collagen, which is the major protein component of the bone extracellular matrix (ECM). The genes displaying the most statistically significant co-expression link to COL1A1 are ASPN, TGFB1, DKK1, IL-6, TENM3 and GDF5. DKK1, FRZB and WISP3 are components of the Wnt signaling pathway. CX3CR1 and GDF5 regulate chondrogenesis through the canonical Wnt signaling pathway. ASPN could induce collagen mineralization through binding with collagen and calcium. Integrated bioinformatics analysis indicates that ECM, Wnt signaling pathway and TGF-β signaling pathway are involved in the occurrence of DDH. These provide a basis for further exploring the pathogenesis of DDH.","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41517022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genetic constraint metrics such as the gnomAD probability of being loss-of-function (LoF) intolerant (pLI) are used to prioritize candidate genes but the mode of inheritance of highly constrained genes has never specifically been studied. We compared 605 genes with a pLI of 1 (pLI1 group) with a random sample of 635 genes from gnomAD (the random group) in terms of genetic constraint metrics, associations with Mendelian disease, modes of inheritance, and two intragenic constraint scores: the percentage of constraint coding regions (CCR) in the 99th percentile and the gene variation intolerance rank (GeVIR). The proportion of genes associated with a Mendelian disease was 35.9% (217/605) in the pLI1 group and 19.5% (124/635) in the random group (p < 0.0001). The modes of inheritance in the random group were autosomal dominant for 35 genes (28.2%), autosomal recessive for 69 (55.6%), mixed for 14 (11.3%) and X-linked for 6 genes (4.8%). The corresponding distribution in the pLI1 group was 150 (69.1%), 26 (12.0%), 14 (6.5%) and 27 (12.4%) (p < 0.0001). The percentage of CCRs in the 99th percentile was 0.3 in the random group versus 1.12 in the pLI1 group (p < 0.0001). The GeVIR score was 50.9 for the random group versus 15.1 for the pLI1 group (p < 0.0001). High genetic constraint does not seem to be associated with a particular mode of inheritance but does seem to be associated with the intragenic constraint scores considered here. Some highly constrained genes are associated with two different modes of inheritance.
{"title":"No preferential mode of inheritance for highly constrained genes.","authors":"Alexandre Fabre, Julien Mancini","doi":"10.5582/irdr.2022.01011","DOIUrl":"https://doi.org/10.5582/irdr.2022.01011","url":null,"abstract":"Genetic constraint metrics such as the gnomAD probability of being loss-of-function (LoF) intolerant (pLI) are used to prioritize candidate genes but the mode of inheritance of highly constrained genes has never specifically been studied. We compared 605 genes with a pLI of 1 (pLI1 group) with a random sample of 635 genes from gnomAD (the random group) in terms of genetic constraint metrics, associations with Mendelian disease, modes of inheritance, and two intragenic constraint scores: the percentage of constraint coding regions (CCR) in the 99th percentile and the gene variation intolerance rank (GeVIR). The proportion of genes associated with a Mendelian disease was 35.9% (217/605) in the pLI1 group and 19.5% (124/635) in the random group (p < 0.0001). The modes of inheritance in the random group were autosomal dominant for 35 genes (28.2%), autosomal recessive for 69 (55.6%), mixed for 14 (11.3%) and X-linked for 6 genes (4.8%). The corresponding distribution in the pLI1 group was 150 (69.1%), 26 (12.0%), 14 (6.5%) and 27 (12.4%) (p < 0.0001). The percentage of CCRs in the 99th percentile was 0.3 in the random group versus 1.12 in the pLI1 group (p < 0.0001). The GeVIR score was 50.9 for the random group versus 15.1 for the pLI1 group (p < 0.0001). High genetic constraint does not seem to be associated with a particular mode of inheritance but does seem to be associated with the intragenic constraint scores considered here. Some highly constrained genes are associated with two different modes of inheritance.","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47390659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabry disease (FD) is a rare lysosomal storage disease. FD is caused by the presence of a deleterious mutation in the GLA gene encoding the enzyme alpha galactosidase A (αGAL A) on the X chromosome. The accumulation of Gb3 and lyso-GL-3 in nerve fiber cells, endothelium, vascular muscle cells, mesangial cells, podocytes, renal tubular epithelial cells and cardiomyocytes is the most important pathogenetic factor. The rate of disease progression depends on residual conserved enzymatic activity. In this article we present an example of a 25-year-old patient with FD with an initial asymptomatic course. The first manifestation of FD developed in the third decade of life. These include high blood pressure, urinary changes and grade V renal failure, requiring renal replacement therapy. The diagnosis was made very late, when renal failure and cerebro-cardiac complications occurred, including stroke and dangerous cardiac tamponade.
{"title":"Fabry disease - a genetically conditioned extremely rare disease with a very unusual course.","authors":"M. Śnit, Marcela Przyłudzka, W. Grzeszczak","doi":"10.5582/irdr.2021.01132","DOIUrl":"https://doi.org/10.5582/irdr.2021.01132","url":null,"abstract":"Fabry disease (FD) is a rare lysosomal storage disease. FD is caused by the presence of a deleterious mutation in the GLA gene encoding the enzyme alpha galactosidase A (αGAL A) on the X chromosome. The accumulation of Gb3 and lyso-GL-3 in nerve fiber cells, endothelium, vascular muscle cells, mesangial cells, podocytes, renal tubular epithelial cells and cardiomyocytes is the most important pathogenetic factor. The rate of disease progression depends on residual conserved enzymatic activity. In this article we present an example of a 25-year-old patient with FD with an initial asymptomatic course. The first manifestation of FD developed in the third decade of life. These include high blood pressure, urinary changes and grade V renal failure, requiring renal replacement therapy. The diagnosis was made very late, when renal failure and cerebro-cardiac complications occurred, including stroke and dangerous cardiac tamponade.","PeriodicalId":14420,"journal":{"name":"Intractable & rare diseases research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47131837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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