A systematic review assessing the existence of pneumothorax-only variants of FLCN. Implications for lifelong surveillance of renal tumours

AbstractIndividuals with Birt–Hogg–Dubé syndrome (BHDS) may develop fibrofolliculomas, pneumothorax and/or renal cell carcinoma (RCC). Currently, all patients with pathogenic FLCN variants are recommended to have renal surveillance. It has however been suggested that some FLCN variants only cause pneumothorax, which would make surveillance unnecessary in certain cases. This review assesses this possibility. We provide an up-to-date analysis of clinical and genetic features of BHDS. The PUBMED database was systematically searched to find all articles describing patients with pathogenic FLCN variants. The relevant clinical and genetic features of these patients were recorded and analysed. The prevalence of pneumothorax, pulmonary cysts, RCC and characteristic skin lesions in BHDS were 50.9% (n = 1038), 91.9% (n = 720), 22.5% (n = 929) and 47.9% (n = 989), respectively. There was a higher prevalence of pneumothoraces (p < 0.0001) but lower prevalence of dermatological findings (p < 0.0001) in patients from East Asia compared to North America or Europe. Of the 194 pathogenic FLCN variants, 76 could be defined as ‘pneumothorax-only’. Pneumothorax only pathogenic variants (POPVs) were distributed throughout the gene, and there were no statistical differences in variant type. The majority of POPVs (65/76) affected no more than three individuals. Individuals with ‘POPVs’ also tended to be younger (45 vs. 47 years, p < 0.05). Many apparent POPVs in the literature could result from variable expressivity, age-related penetrance and other confounding factors. We therefore recommend that all individuals found to carry a pathogenic FLCN variant be enroled in lifelong surveillance for RCC.

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Novel Folliculin Gene Mutations in Polish Patients With Birt-hogg-dubé Syndrome

10.21203/rs.3.rs-294782/v1 ◽

2021 ◽

Author(s):

Elzbieta Radzikowska ◽

Urszula Lechowicz ◽

Jolanta Winek ◽

Lucyna Opoka

Keyword(s):

Gene Mutations ◽

Skin Lesions ◽

Renal Angiomyolipoma ◽

Inherited Disease ◽

First Case ◽

Renal Tumours ◽

Pulmonary Cysts ◽

Frequent Mutations ◽

History Of ◽

The Mean

Abstract Birt-Hogg-Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS.Materials and MethodsThe first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations.ResultsBHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41). ConclusionsAll analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified.

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Birt-Hogg-Dubé syndrome presenting with spontaneous pneumothorax and extensive pulmonary cysts in the absence of skin lesions or renal pathology

BMJ Case Reports ◽

10.1136/bcr-2019-231039 ◽

2019 ◽

Vol 12 (9) ◽

pp. e231039

Author(s):

Kartik Kumar ◽

Clare Ross

Keyword(s):

Spontaneous Pneumothorax ◽

Autosomal Dominant ◽

Skin Lesions ◽

Lung Cysts ◽

Cystic Lung ◽

Increased Risk ◽

Renal Tumours ◽

Pulmonary Cysts ◽

Dominant Condition ◽

Bhd Syndrome

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition which classically manifests with skin lesions such as fibrofolliculomas, pulmonary cysts that predispose to spontaneous pneumothorax and an increased risk of developing renal cell carcinoma. We describe the case of a patient who presented with a spontaneous pneumothorax on a background of multiple lung cysts, in the absence of cutaneous fibrofolliculomas and renal tumours. A germline mutation in the folliculin FLCN gene was subsequently identified, confirming BHD syndrome. Our case highlights the importance of considering a broad differential diagnosis for the cause of a spontaneous pneumothorax in the presence of unexplained cystic lung disease and emphasises the value of maintaining a high index of clinical suspicion for inherited causes of pneumothoraces.

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Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01931-0 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Elżbieta Radzikowska ◽

Urszula Lechowicz ◽

Jolanta Winek ◽

Lucyna Opoka

Keyword(s):

Gene Mutations ◽

Skin Lesions ◽

Renal Angiomyolipoma ◽

Inherited Disease ◽

First Case ◽

Renal Tumours ◽

Pulmonary Cysts ◽

Frequent Mutations ◽

History Of ◽

The Mean

Abstract Background Birt–Hogg–Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS. Materials and methods The first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations. Results BHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41). Conclusions All analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified.

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Changes in aqueous and vitreous inflammatory cytokine levels in neovascular age-related macular degeneration: A systematic review and meta-analysis

10.26226/morressier.5e61463c250f7ee26aeb41ed ◽

2020 ◽

Author(s):

Samuel Minaker

Keyword(s):

Systematic Review ◽

Macular Degeneration ◽

Inflammatory Cytokine ◽

Meta Analysis ◽

Age Related Macular Degeneration ◽

Age Related ◽

Cytokine Levels

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Faculty of 1000 evaluation for A systematic review on zinc for the prevention and treatment of age-related macular degeneration.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.718008525.793478652 ◽

2013 ◽

Author(s):

David Boyer

Keyword(s):

Systematic Review ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Age Related ◽

Prevention And Treatment

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Socioeconomic and Demographic Statuses as Determinants of Adherence to Antiretroviral Treatment in HIV Infected Patients: A Systematic Review of the Literature

Current HIV Research ◽

10.2174/1570162x17666190919130229 ◽

2019 ◽

Vol 17 (3) ◽

pp. 161-172 ◽

Cited By ~ 2

Author(s):

Nuredin Nassir Azmach ◽

Temam Abrar Hamza ◽

Awel Abdella Husen

Keyword(s):

Systematic Review ◽

Occupational Status ◽

Original Research ◽

Positive Trend ◽

Hiv Patients ◽

Aids Patients ◽

Pubmed Database ◽

Education And Employment ◽

Socio Economic Factors ◽

Hiv Aids

Background: Socioeconomic and demographic statuses are associated with adherence to the treatment of patients with several chronic diseases. However, there is a controversy regarding their impact on adherence among HIV/AIDS patients. Thus, we performed a systematic review of the evidence regarding the association of socioeconomic and demographic statuses with adherence to antiretroviral therapy (ART) among HIV/AIDS patients. Methods: The PubMed database was used to search and identify studies concerning about socioeconomic and demographic statuses and HIV/AIDS patients. Data were collected on the association between adherence to ART and varies determinants factors of socioeconomic (income, education, and employment/occupation) and socio-demographic (sex and age). Findings: From 393 potentially-relevant articles initially identified, 35 original studies were reviewed in detail, which contained data that were helpful in evaluating the association between socioeconomic/ demographic statuses and adherence to ART among HIV patients. Two original research study has specifically focused on the possible association between socioeconomic status and adherence to ART. Income, level of education, and employment/occupational status were significantly and positively associated with the level of adherence in 7 studies (36.8%), 7 studies (28.0%), and 4 studies (23.5%) respectively out of 19, 25, and 17 studies reviewed. Sex (being male), and age (per year increasing) were significantly and positively associated with the level of adherence in 5 studies (14.3%), and 9 studies (25.7%) respectively out of 35 studies reviewed. However, the determinant of socioeconomic and demographic statuses was not found to be significantly associated with adherence in studies related to income 9(47.4%), education 17(68.0%), employment/ occupational 10(58.8%), sex 27(77.1%), and age 25(71.4%). Conclusion: The majority of the reviewed studies reported that there is no association between socio- demographic and economic variables and adherence to therapy. Whereas, some studies show that age of HIV patients (per year increasing) and sex (being male) were positively associated with adherence to ART. Among socio-economic factors, the available evidence does not provide conclusive support for the existence of a clear association with adherence to ART among HIV patients. There seems to be a positive trend between socioeconomic factors and adherence to ART in some of the reviewed studies.

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Pathogenesis of Age-related Cataract: a systematic review of proteomic studies

Current Proteomics ◽

10.2174/1570164617999201020205100 ◽

2020 ◽

Vol 17 ◽

Author(s):

Christina Karakosta ◽

Argyrios Tzamalis ◽

Michalis Aivaliotis ◽

Ioannis Tsinopoulos

Keyword(s):

Systematic Review ◽

Oxidant Stress ◽

Critical Role ◽

Human Lens ◽

Nuclear Cataract ◽

Cataract Formation ◽

Post Translational Modification ◽

Ability To Act ◽

Age Related

Background/Objective:: The aim of this systematic review is to identify all the available data on human lens proteomics with a critical role to age-related cataract formation in order to elucidate the physiopathology of the aging lens. Materials and Methods:: We searched on Medline and Cochrane databases. The search generated 328 manuscripts. We included nine original proteomic studies that investigated human cataractous lenses. Results:: Deamidation was the major age-related post-translational modification. There was a significant increase in the amount of αA-crystallin D-isoAsp58 present at all ages, while an increase in the extent of Trp oxidation was apparent in cataract lenses when compared to aged normal lenses. During aging, enzymes with oxidized cysteine at critical sites included GAPDH, glutathione synthase, aldehyde dehydrogenase, sorbitol dehydrogenase, and PARK7. Conclusion:: D-isoAsp in αA crystallin could be associated with the development of age-related cataract in human, by contributing to the denaturation of a crystallin, and decreasing its ability to act as a chaperone. Oxidation of Trp may be associated with nuclear cataract formation in human, while the role of oxidant stress in age-related cataract formation is dominant.

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Covid-19 and Autoimmune Diseases: A Systematic Review of Reported Cases

Current Rheumatology Reviews ◽

10.2174/1573397116666201029155856 ◽

2020 ◽

Vol 16 ◽

Author(s):

Mariam Ahmed Saad ◽

Mostafa Alfishawy ◽

Mahmoud Nassar ◽

Mahmoud Mohamed ◽

Ignatius N Esene ◽

...

Keyword(s):

Systematic Review ◽

Autoimmune Disease ◽

Kawasaki Disease ◽

Autoimmune Diseases ◽

English Language ◽

Clinical Evidence ◽

Eligibility Criteria ◽

Thrombocytopenic Purpura ◽

Pubmed Database ◽

Viral Illness

Introduction: Over 4.9 million cases of Coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide pandemic began. Since the emergence of COVID-19, a number of confirmed cases reported autoimmune manifestations. Herein, we reviewed the reported COVID-19 cases with associated autoimmune manifestations. Methods: We searched PubMed database using all available keyword for COVID-19. All related studies between January 1st, 2020 to May 22nd, 2020 were reviewed. Only studies published in English language were considered. Articles were screened based on titles and abstract. All reports of confirmed COVID-19 patients who have associated clinical evidence of autoimmune disease were selected. Results: Among 10006 articles, searches yielded, Thirty-two relevant articles for full-text assessment. Twenty studies meet the eligibility criteria. The twenty eligible articles reported 33 cases of confirmed COVID-19 diagnosis who developed an autoimmune disease after the onset of covid-19 symptoms. Ages of patients varied from a 6 months old infant to 89 years old female (Mean=53.9 years of 28 cases); five cases had no information regarding their age. The time between symptoms of viral illness and onset of autoimmune symptoms ranged from 2 days to 33 days (Mean of the 33 cases=9.8 days). Autoimmune diseases were one case of subacute thyroiditis (3%), two cases of Kawasaki Disease (6.1%), three cases of coagulopathy and antiphospholipid syndrome (9.1%), three cases of immune thrombocytopenic purpura (9.1%), eight cases of autoimmune hemolytic anemia (24.2%), and sixteen cases of Guillain–Barré syndrome (48.5%). Conclusions: COVID-19 has been implicated in the development in a range of autoimmune diseases which may shed a light on the association between autoimmune diseases and infections.

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Efeitos dos Programas de Treinamento Aeróbio, de Força e Combinado na Glicose Sanguínea em Diabéticos do Tipo 2: uma Revisão Sistemática/ Effects of Aerobic, Strength and Combined Programs Training on Blood Glucose in Type 2 Diabetic: a Systematic Review.

REVISTA CIÊNCIAS EM SAÚDE ◽

10.21876/rcsfmit.v5i1.301 ◽

1970 ◽

Vol 5 (1) ◽

pp. 61-74 ◽

Cited By ~ 1

Author(s):

Alexandre de Souza E Silva ◽

Maria Paula Gonçalves Mota

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Type 2 Diabetes ◽

Blood Glucose ◽

Training Program ◽

Aerobic Training ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Pubmed Database

O trabalho tem como objetivo analisar os estudos que avaliaram os efeitos dos programas de treinamento aeróbio, força e combinado nos níveis de glicose sanguínea em indivíduos com diabetes do tipo 2. Foi utilizado o método de revisão sistemática, sendo utilizada a base de dados PubMed. As palavras chaves utilizadas para pesquisa foram training and diabetes. Foram identificados 484 artigos originais. Apenas 17 estudos respeitaram os critérios de inclusão. Os resultados evidenciam que os programas de treinamento aeróbio diminuíram os níveis de glicose. O programa de treinamento de força também foi favorável à diminuição dos níveis de glicose sanguínea. Já o programa de treinamento combinado não demonstrou efeitos favoráveis no controle da glicose sanguínea. Conclui-se que o programa de treinamento aeróbio e de força ajudam a controlar os níveis de glicose sanguínea em indivíduos com diabetes do tipo 2. Palavras-chave: diabetes mellitus, treinamento, glicose.ABSTRACTThe study aims to analyze the studies that evaluated the effects of aerobic, strength and combined programs training in blood glucose levels in people with type 2 diabetes. We used a systematic review method and is used to PubMed database. The key words used for searching were training and diabetes. We identified 484 original articles. Only 17 studies complied with the inclusion criteria. The results show that aerobic training programs decreased glucose levels. The strength training program was also favorable to decrease in blood glucose levels. But the combined training program has not shown favorable effects on blood glucose control. We conclude that the aerobic training and strength helps control blood glucose levels in individuals with type 2 diabetes. Keywords: diabetes mellitus, training, glucose.

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