Molecular Genetics & Genomic Medicine最新文献

{"title":"A Novel Mutation of FOXC1 (P136L) in an Axenfeld-Rieger Syndrome Patient With a Systematized Delusion of Jealousy: A Case Report and Literature Review.","authors":"Yuta Yoshino, Jun-Ichi Iga, Shu-Ichi Ueno","doi":"10.1002/mgg3.70008","DOIUrl":"10.1002/mgg3.70008","url":null,"abstract":"<p><strong>Background: </strong>The main features of Axenfeld-Rieger Syndrome (ARS) are ocular, auditory, neurological, and morphological brain abnormalities. Mutations in forkhead box protein C1 (FOXC1) are among the responsible genes causing ARS, but neuropsychiatric features have rarely been reported. The case of an ARS patient (a 77-year-old man) with delusions of jealousy and impairment of working memory, in addition to the main clinical features, glaucoma and leukoencephalopathy, is presented.</p><p><strong>Methods: </strong>The mutation in the patient's genome was found with whole exome sequencing and in silico analysis using PolyPhen-2 and SIFT. Furthermore, AlphaFold2 and PyMOL were used to predict the protein structure based on the mutation.</p><p><strong>Results: </strong>A novel mutation at the forkhead domain of FOXC1 gene (c.408C>A, p.Phe136Leu) was found and confirmed in the patient's family, and it was predicted to cause protein damage; the SIFT score was 0, meaning deleterious, and the PolyPhen2 result also indicated damaging (score: 0.997). The predicted protein structure based on the novel mutation was different from that of the native structure. In the literature review, 6 of 95 (6.3%) cases showed neuropsychiatric features. Of them, 5 of 6 (83.3%) mutations were located in the forkhead domain.</p><p><strong>Conclusion: </strong>A novel mutation was found in the FOXC1 gene (c.408C>A, p.Phe136Leu), which possibly induces delusions of jealousy and impairment of working memory, as well as features of ARS, by changing the protein structure. Mutations in that domain of the FOXC1 gene may be important not only for ocular abnormalities but also for brain function.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70008"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Splice Site Variant in COL6A1 Causes Ullrich Congenital Muscular Dystrophy in a Consanguineous Malian Family.","authors":"Alassane Baneye Maiga, Ibrahim Pamanta, Salia Bamba, Lassana Cissé, Salimata Diarra, Sidi Touré, Abdoulaye Yalcouyé, Seydou Diallo, Salimata Diallo, Fousseyni Kané, Seybou Hassane Diallo, Hamidou Oumar Ba, Cheick Oumar Guinto, Kenneth Fischbeck, Guida Landoure, Idrissa Ahmadou Cissé","doi":"10.1002/mgg3.70032","DOIUrl":"10.1002/mgg3.70032","url":null,"abstract":"<p><strong>Background: </strong>Congenital muscular dystrophies (CMDs) are diverse early-onset conditions affecting skeletal muscle and connective tissue. This group includes collagen VI-related dystrophies such as Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM), caused by mutations in the COL6A1, COL6A2 and COL6A3 genes. We report a consanguineous Malian family with three siblings affected by UCMD due to a novel homozygous splice site variant in the COL6A1 gene.</p><p><strong>Methods: </strong>After obtaining consent, three affected siblings and their relatives underwent physical examinations by specialists and laboratory tests where possible. DNA was extracted from peripheral blood for genetic testing, including Whole Exome Sequencing (WES). Putative variants were confirmed through Sanger Sequencing and assessed for pathogenicity using in silico tools.</p><p><strong>Results: </strong>The three siblings and their healthy parents, from a consanguineous marriage, presented with early-onset progressive muscle weakness, walking difficulty, proximal motor deficits, severe muscle atrophy, hypotonia, skeletal deformities, joint hyperlaxity, ankyloses at the elbows and knees, keloid scars and dental crowding. No cardiac involvement was detected and creatine kinase (CK) levels were normal. All had low serum calcium levels, treated with oral supplements. Needle myography indicated myopathic patterns. WES identified a novel splice site variant in the first intron of COL6A1 (c.98-1G>C), which segregated with the disease within the family. This variant is predicted to cause exon 2 skipping in COL6A1, with a high CADD score of 33 and Splice AI predicting it as deleterious.</p><p><strong>Conclusion: </strong>We identified a novel COL6A1 variant in a consanguineous family, highlighting the need for further studies in larger African cohorts to enhance genetic epidemiology and prepare for future therapeutic research.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70032"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenicity of the LDLR c.97C>T (p.Gln33Ter) Mutation in Familial Hypercholesterolemia.","authors":"Kaihan Wang, Tingting Hu, Mengmeng Tai, Yan Shen, Shaoyi Lin, Yongjuan Guo, Xiaomin Chen","doi":"10.1002/mgg3.70030","DOIUrl":"10.1002/mgg3.70030","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is a hereditary disease caused mainly by mutations in the gene encoding the low-density lipoprotein receptor (LDLR). This study aimed to confirm the pathogenicity of the LDLR c.97C>T (p.Gln33Ter) mutation through in vitro functional validation and determine whether this nonsense mutation induces nonsense-mediated mRNA decay (NMD).</p><p><strong>Methods: </strong>The proband and his family were included in accordance with Chinese Expert Consensus on FH screening. The disease-causing mutations were fund using whole-exome sequencing and were confirmed using bidirectional Sanger sequencing. The pathogenicity of the mutation was predicted using in silico analysis. The LDLR c.97C>T (p.Gln33Ter) mutation was generated using site-directed mutagenesis and expressed in HEK293T cells lacking endogenous LDLR expression. The effects of this alteration on LDLR expression and LDL uptake were assessed using flow cytometry, quantitative polymerase chain analysis, western blotting, and confocal laser scanning microscopy.</p><p><strong>Results: </strong>The mutation that causes FH in this family was LDLR c.97C>T (p.Gln33Ter), and family members with this mutation exhibited elevated levels of low-density lipoprotein cholesterol (LDL-C). The cell experiment results showed that this mutation prevented the synthesis of LDLR protein and caused the cells to lose their LDL uptake ability.</p><p><strong>Conclusion: </strong>LDLR c.97C>T (p.Gln33Ter) is a pathogenic FH mutation. However, this nonsense mutation did not induce NMD.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70030"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Synonymous Variant in SQSTM1 Causes Neurodegeneration With Ataxia, Dystonia, and Gaze Palsy Revealed by Urine-Derived Cells-Based Functional Analysis.","authors":"Shinji Masuko, Mitsuto Sato, Katsuya Nakamura, Kohei Hamanaka, Satoko Miyatake, Yuji Inaba, Tomoki Kosho, Naomichi Matsumoto, Yoshiki Sekijima","doi":"10.1002/mgg3.70044","DOIUrl":"10.1002/mgg3.70044","url":null,"abstract":"<p><strong>Background: </strong>Heterozygous variants of sequestosome-1 gene (SQSTM1) have been reported in patients with various neurological disorders, whereas biallelic pathogenic variants of SQSTM1 can cause child-onset and multisystem neurodegeneration, including cerebellar ataxia, dystonia, and vertical gaze palsy (NADGP). Here, we describe two cases of NADGP in a Japanese family.</p><p><strong>Methods: </strong>We performed clinical and genetic laboratory evaluations of the two patients and their healthy parents.</p><p><strong>Results: </strong>By whole-exome sequencing, we identified compound heterozygous variants in SQSTM1(NM_003900.5): c.1A>G p.(Met1?) in the initial codon, and c.969G>A, located at the 3' end of exon 6, which is novel and seemingly a synonymous but is actually a truncating variant causing aberrant splicing. An SQSTM1 protein expression assay using urine-derived cells (UDCs) demonstrated that both variants (c.1A>G and c.969G>A) were unable to induce normal splicing of premessenger RNA. Cerebellar ataxia is a characteristic manifestation of this disorder; however, brain magnetic resonance imaging studies have not shown significant cerebellar atrophy. Our patients experienced chorea during adolescence.</p><p><strong>Conclusions: </strong>Only a few reports have highlighted the presence of chorea; however, our findings suggest that NADGP should be considered as a differential diagnosis of hereditary chorea. This study also demonstrates the utility of UDCs, obtained using noninvasive approaches, in functionally analyzing genetic diseases.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70044"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11588856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Myocardial Fibrosis in Marfan Syndrome Using Cardiac Magnetic Resonance Imaging.","authors":"Anthony Demolder, Dan Devos, Julie De Backer, Laura Muiño-Mosquera","doi":"10.1002/mgg3.70024","DOIUrl":"10.1002/mgg3.70024","url":null,"abstract":"<p><strong>Background: </strong>Impaired myocardial function and arrhythmia are important manifestations of Marfan syndrome (MFS). Studies assessing myocardial fibrosis in relation to these manifestations are scarce.</p><p><strong>Methods: </strong>This cross-sectional, single-center study assessed ventricular volumes, ventricular function, and myocardial fibrosis by cardiac magnetic resonance imaging (CMR) in patients with MFS harboring a (likely) pathogenic FBN1 variant. The presence and extent of fibrosis were assessed by late gadolinium enhancement (LGE) and extracellular volume measurement (ECV). Data on 24-h Holter monitoring and clinical data were extracted from electronic patient records.</p><p><strong>Results: </strong>The study included 32 unselected patients with MFS (median age 38 years [range 10-69], 41% women). No focal myocardial fibrosis was detected. Six patients (21%) had diffuse fibrosis (ECV > 29%). No association was found between the presence of diffuse fibrosis and clinically relevant myocardial dysfunction. Five patients (16%) had reduced left ventricular ejection fraction (LVEF < 55%). While all of these exhibited mitral annular disjunction (MAD), only two had ECV > 29%. Patients with MAD had increased indexed LV volumes (median end-diastolic volume, 92 mL/m² [IQR, 78-100] vs. 78 mL/m² [IQR, 71-87]; median end-systolic volume, 31 mL/m² [IQR, 23-46] vs. 22 mL/m² [IQR, 21-28]), also after adjusting for the presence of mitral and aortic valve regurgitation. No differences in ECV were seen between patients with and without MAD.</p><p><strong>Conclusions: </strong>In this cohort of patients with MFS, focal myocardial fibrosis was not detected using CMR. Although diffuse fibrosis was observed in 21% of patients, no evident connection to clinically relevant myocardial dysfunction was found. Further studies should evaluate the impact of diffuse fibrosis on clinical outcome prediction.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70024"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Growth Patterns in Korean Children With Sotos Syndrome Through the Development of a Disease-Specific Growth Chart.","authors":"Naye Choi, Hwa Young Kim, Jung Min Ko","doi":"10.1002/mgg3.70028","DOIUrl":"10.1002/mgg3.70028","url":null,"abstract":"<p><strong>Background: </strong>Sotos syndrome (SS) is a rare disorder characterized by overgrowth, distinctive facial features, and intellectual disability that is primarily caused by NSD1 pathogenic variants or 5q35 microdeletions.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical characteristics and 339 anthropometric measurements over an average of 4.3 years of follow-up in 57 Korean children with SS. Sex-specific percentile curves for height, weight, and head circumference were developed using a generalized additive model that included factors such as location, scale, and shape.</p><p><strong>Results: </strong>Males with SS demonstrated higher height before the age of 12.0, greater weight before 10.0, and larger head circumference before 15.5 compared to age- and sex-matched controls. Females with SS displayed higher height before 17.0, greater weight before 10.5, and larger head circumference before 12.0 compared to controls. Bone age was advanced compared to chronological age in 40% of males and 8% of females at their last visit. The predicted and target adult heights were not significantly different between groups. In subgroup analysis, the intragenic variant group (n = 48) showed a higher mean standard deviation score of height and weight in males, and head circumference in females compared to the microdeletion group (n = 9).</p><p><strong>Conclusions: </strong>Korean children with genetically confirmed SS exhibited overgrowth in height, weight, and head circumference. Overgrowth phenotypes were more prominent in patients with NSD1 intragenic variants than in those with microdeletions. This is the first study to provide reference data on the growth of Korean children with SS.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70028"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERAP1 Gene Variants and Haplotypes Associated With Psoriasis Vulgaris of Han Chinese in Inner Mongolia.","authors":"Xin Li, Jia Bao, Liya Ai, Fan-Rui Yang, Bo Yu, Yan-Ping Huang, Na Li, Wen-Yuan Ding, Zhi-Qiang Sun, Xin-Xiang Lv, Jian-Wen Han","doi":"10.1002/mgg3.70021","DOIUrl":"10.1002/mgg3.70021","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the association between genetic variants of ERAP1 (OMIM: 606832) and psoriasis vulgaris (PsV) susceptibility in Inner Mongolia Han nationality.</p><p><strong>Methods: </strong>For primary screening, the subjects included 142 PsV cases and 100 healthy controls without psoriasis. The 27 exons of ERAP1 gene were sequenced to screen significant genetic variants. For the validation study, the subjects included 1030 PsV cases and 965 healthy controls. A total of 18 mutations were detected for genetic variants of significance in primary screening and previously reported genetic variants.</p><p><strong>Results: </strong>In primary screening stage, 13 genetic variants of ERAP1 showed an association with psoriasis. A total of 18 genetic variants were typed for the validation, and 12 genetic variants were associated with PsV in Inner Mongolia Han population. Stratified analysis showed significant differences in the allele frequencies of 8 ERAP1 genetic variants in cases with positive family history, and significant differences in allele frequencies among 9 ERAP1 genetic variants in patients with negative family history. A risk haplotype (TCCCTCCAGACC) was significantly associated with PsV, and the most risk haplotype was E730/K528/R127/E56.</p><p><strong>Conclusion: </strong>ERAP1 gene mutation may be associated with PsV and HLA-C*06:02 in Han nationality in Inner Mongolia. A risk haplotype of four-nonsynonymous mutation (E730/K528/R127/E56) is associated with PsV.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70021"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Read Sequencing Identifying the Genetic Complexity of Congenital Adrenal Hyperplasia in the Pedigree.","authors":"Ximin Chen, Jing Zhao, Danhua Li, Na Xi, Danying Yi, Mengjia Yan, Yan Yin, Xueyan Wang","doi":"10.1002/mgg3.70029","DOIUrl":"10.1002/mgg3.70029","url":null,"abstract":"<p><strong>Background: </strong>High sequence homology between CYP21A2 and CYP21A1P poses challenges to genetic diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). Traditional genetic testing is unable to provide an accurate diagnosis due to the genetic complexity of CAH.</p><p><strong>Methods: </strong>Deletions, duplications, and recombination breakpoints were precisely identified by long-read sequencing (LRS).</p><p><strong>Results: </strong>This study presented a pregnant woman, a 21-OHD carrier detected by MLPA, and her husband, a normal subject also detected by MLPA. The fetus was suspected of having 21-OHD based on clinical presentations such as enlarged adrenal glands, atypical external genitalia and karyotyping of 46, XX. LRS further identified the fetus as having the most severe salt-wasting (SW) form of 21-OHD with a compound heterozygote genotype. One allele was TNXA/TNXB CH-2, while the other allele was CYP21A1P/CYP21A2 CH-8. LRS precisely determined the genotypes of the fetus's father and grandmother with duplications, which misdiagnosed by MLPA. The multidisciplinary team recommended immediate glucocorticoid and mineralocorticoid treatment for the child after birth to prevent life-threatening adrenal crisis.</p><p><strong>Conclusions: </strong>LRS provides precise diagnosis for family members with CYP21A2 deletion or duplication, improving disease management and preventing potential adrenal crises. When used in pre-pregnancy genetic testing, LRS can indicate high genetic risk and guide the appropriate therapy during pregnancy and immediately after birth.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70029"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newborn Screening for Isovaleric Acidemia: Treatment With Pivalate-Generating Antibiotics Contributed to False C5-Carnitine Positivity in a Chinese Population.","authors":"Wei Zhou, Ting Huang, Huizhong Li, Maosheng Gu","doi":"10.1002/mgg3.70034","DOIUrl":"10.1002/mgg3.70034","url":null,"abstract":"<p><strong>Background: </strong>Newborn screening (NBS) for isovaleric acidemia (IVA) is implemented via tandem mass spectrometry (MS/MS), but false-positive results are still common. In addition, NBS for IVA is limited by a lack of suitable biomarkers, especially after the use of pivaloylester-containing antibiotics.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study to explore the clinical correlation between antibiotic administration and false-positive results for isovalerylcarnitine (C5).</p><p><strong>Results: </strong>A total of 509,313 newborns were recruited from the initial NBS study, only one of whom underwent genetic confirmation, conducted between 2015 and 2020. Significant associations between false-positive C5-carnitine screening results and treatment with pivalate-generating antibiotics were identified with retrospective analysis.</p><p><strong>Conclusions: </strong>The current results highlight the detrimental effects of false-positive C5-carnitine screening results. Unless the licensing of pivalate-generating antibiotics for use during the neonatal period is reconsidered, a second-tier test for C5 determination will be necessary.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70034"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers and Facilitators to Participation in Clinical Trials Related to Familial Frontotemporal Dementia: A Qualitative Study.","authors":"David Zammitt, Emilie V Brotherhood, Caroline Fearn, Caroline Greaves, Ollie Hayes, Emma Harding, Madalena Lykourgos, Jonathan D Rohrer, Josh Stott","doi":"10.1002/mgg3.70038","DOIUrl":"10.1002/mgg3.70038","url":null,"abstract":"<p><strong>Aims: </strong>Familial frontotemporal dementia (fFTD) is an inherited neurodegenerative condition characterised by executive dysfunction, impairments in social cognition, behaviour and language. Although no disease-modifying interventions are currently available, several treatments are undergoing clinical trials. This study sought to understand the barriers and facilitators to taking part in such trials, as well as general perceptions of the treatments undergoing trial.</p><p><strong>Method: </strong>Twelve interviews took place with fourteen participants: eight individuals who were genetically at-risk of developing fFTD, two individuals diagnosed with fFTD and four spousal carers. Their views and experiences of clinical trials were explored using thematic analysis.</p><p><strong>Results: </strong>Five main themes were developed: (1) effects on the individual, (2) implications for others, (3) systemic considerations, (4) the impact of genetic status and disease progression and (5) the role of communication and understanding.</p><p><strong>Conclusions: </strong>The decision to participate in clinical trials was said to be complex, involving consideration of logistical barriers alongside health implications. Participants identified potential advantages of participating in clinical trials to be direct health benefits and the ability to help others, however risks to participants and their families' physical and psychological wellbeing were also named. Relationships between organisations and participants were consistently considered to be important, with lack of psychological care at various timepoints post diagnosis; unclear communication and expectation-setting; and inadequate organisational collaboration all identified as barriers. Participants indicated that increased health-professional interest in FTD and an associated increase in opportunities would be key facilitators for greater participation in clinical trials.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70038"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}