Molecular Genetics & Genomic Medicine最新文献

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A Novel Synonymous Variant in SQSTM1 Causes Neurodegeneration With Ataxia, Dystonia, and Gaze Palsy Revealed by Urine-Derived Cells-Based Functional Analysis. 基于尿液衍生细胞的功能分析揭示 SQSTM1 的新型同义变异会导致共济失调、肌张力障碍和凝视麻痹的神经变性。
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-11-01 DOI: 10.1002/mgg3.70044
Shinji Masuko, Mitsuto Sato, Katsuya Nakamura, Kohei Hamanaka, Satoko Miyatake, Yuji Inaba, Tomoki Kosho, Naomichi Matsumoto, Yoshiki Sekijima
{"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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of Myocardial Fibrosis in Marfan Syndrome Using Cardiac Magnetic Resonance Imaging. 利用心脏磁共振成像评估马凡综合征的心肌纤维化。
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-11-01 DOI: 10.1002/mgg3.70024
Anthony Demolder, Dan Devos, Julie De Backer, Laura Muiño-Mosquera
{"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/m<sup>2</sup> [IQR, 78-100] vs. 78 mL/m<sup>2</sup> [IQR, 71-87]; median end-systolic volume, 31 mL/m<sup>2</sup> [IQR, 23-46] vs. 22 mL/m<sup>2</sup> [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}
引用次数: 0
Deciphering Growth Patterns in Korean Children With Sotos Syndrome Through the Development of a Disease-Specific Growth Chart. 通过开发疾病特异性生长曲线图解读韩国索托斯综合征患儿的生长模式
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-11-01 DOI: 10.1002/mgg3.70028
Naye Choi, Hwa Young Kim, Jung Min Ko
{"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}
引用次数: 0
ERAP1 Gene Variants and Haplotypes Associated With Psoriasis Vulgaris of Han Chinese in Inner Mongolia. 与内蒙古汉族银屑病相关的 ERAP1 基因变异和单倍型
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-11-01 DOI: 10.1002/mgg3.70021
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
{"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}
引用次数: 0
Long-Read Sequencing Identifying the Genetic Complexity of Congenital Adrenal Hyperplasia in the Pedigree. 长读测序鉴定先天性肾上腺皮质增生症的复杂遗传基因
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-11-01 DOI: 10.1002/mgg3.70029
Ximin Chen, Jing Zhao, Danhua Li, Na Xi, Danying Yi, Mengjia Yan, Yan Yin, Xueyan Wang
{"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}
引用次数: 0
Newborn Screening for Isovaleric Acidemia: Treatment With Pivalate-Generating Antibiotics Contributed to False C5-Carnitine Positivity in a Chinese Population. 新生儿异戊酸血症筛查:在中国人群中,使用产生特戊酸盐的抗生素会导致 C5-肉碱假阳性。
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-11-01 DOI: 10.1002/mgg3.70034
Wei Zhou, Ting Huang, Huizhong Li, Maosheng Gu
{"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}
引用次数: 0
Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures. ADSSL1 同源缺义变异兄弟姐妹疾病严重程度的差异:临床遗传学研究与文献综述。
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-11-01 DOI: 10.1002/mgg3.70041
Hui Wang, Ting Zhang, Yanming Xu, Wenhui Fan
{"title":"Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures.","authors":"Hui Wang, Ting Zhang, Yanming Xu, Wenhui Fan","doi":"10.1002/mgg3.70041","DOIUrl":"https://doi.org/10.1002/mgg3.70041","url":null,"abstract":"<p><strong>Background: </strong>Distal myopathies are genetic muscle disorders caused by mutations in various genes. A study found that mutations in adenylosuccinate synthetase-like 1 (ADSSL1) are associated with distal myopathy in nine patients from six unrelated families in South Korea. Previous research showed that affected individuals experienced distal muscle weakness starting in adolescence, along with mild facial muscle weakness, slightly elevated or normal serum creatine kinase (CK) levels, and the presence of a few rimmed vacuoles in muscle fibers or minimal chronic myopathic damage. Previously reported patients in this category exhibited an early age of symptom onset and severe muscle weakness. In this study, we present a case of two sisters who share the same mutation locus but display distinct disease phenotypes.</p><p><strong>Methods: </strong>A literature review was conducted on distal myopathies in patients with ADSSL1 mutations, alongside a retrospective analysis of disease severity variability among siblings with a homozygous missense variant of ADSSL1.</p><p><strong>Results: </strong>The study focuses on two sisters with differing disease manifestations despite carrying the same genetic mutation. The older sister showed lower ability in running and jumping compared to her peers at age 7 and experienced notable muscle weakness and atrophy by age 27, whereas the younger sister remained free of symptoms at age 30.</p><p><strong>Conclusion: </strong>These findings suggest that mutations at the same locus can result in varying disease outcomes, emphasizing the complexity of predicting disease progression based solely on genetic mutations.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70041"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Barriers and Facilitators to Participation in Clinical Trials Related to Familial Frontotemporal Dementia: A Qualitative Study. 参与家族性额颞叶痴呆症相关临床试验的障碍和促进因素:定性研究。
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-11-01 DOI: 10.1002/mgg3.70038
David Zammitt, Emilie V Brotherhood, Caroline Fearn, Caroline Greaves, Ollie Hayes, Emma Harding, Madalena Lykourgos, Jonathan D Rohrer, Josh Stott
{"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}
引用次数: 0
Molecular Pathology of Myotonic Dystrophy Type 1 in Iceland. 冰岛 1 型肌营养不良症的分子病理学。
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-10-01 DOI: 10.1002/mgg3.70013
E G Hallgrímsdóttir, H Svansson, V F Stefánsdóttir, Ó Á Sveinsson, H Ólafsdóttir, E Briem, S Sveinbjörnsdóttir, J J Jónsson
{"title":"Molecular Pathology of Myotonic Dystrophy Type 1 in Iceland.","authors":"E G Hallgrímsdóttir, H Svansson, V F Stefánsdóttir, Ó Á Sveinsson, H Ólafsdóttir, E Briem, S Sveinbjörnsdóttir, J J Jónsson","doi":"10.1002/mgg3.70013","DOIUrl":"10.1002/mgg3.70013","url":null,"abstract":"<p><strong>Background: </strong>Myotonic Dystrophy type 1 (DM1) is an autosomal dominant disease with anticipation due to increased number of CTG repeats in the DMPK gene.</p><p><strong>Methods: </strong>This retrospective, cohort study in Iceland assessed prevalence of DM1, molecular pathology, and patient ascertainment. Data was collected from all major hospitals in Iceland, Medical Director of Health, and independent clinics. Cohort criteria were diagnosis of DM1 on January 1, 2021, or time of death. Population-based Icelandic Genealogy Database of the Genetical Committee at the University of Iceland was used for genealogy.</p><p><strong>Results: </strong>In Iceland, 221 individuals, including 19 obligate carriers, had been diagnosed with DM1 of which 144 were alive giving a point prevalence of 39 per 100,000 (four times the world average of 9.3). Genealogy analysis identified 45 first-degree families. Age-adjusted prevalence ranged between 11 and 66 per 100,000. Average potential years of life lost were 20.5 per person. Where information was available, 63% of ascertainment was based on family history in cascade testing.</p><p><strong>Conclusion: </strong>The differences in age-adjusted prevalence suggest that the overall point prevalence is an underestimation due to underdiagnosis in younger age groups and lethality in oldest age group. Our data supports use of cascade testing to improve DM1 ascertainment.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 10","pages":"e70013"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381284","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}
引用次数: 0
Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large-Scale Genome-Wide Cross-Trait Analysis. 大疱性类天疱疮与特应性皮炎之间的基因组相关性、共享基因位点和因果关系:大规模全基因组交叉性状分析。
IF 1.5 4区 医学
Molecular Genetics & Genomic Medicine Pub Date : 2024-10-01 DOI: 10.1002/mgg3.70022
Qing Wang, Xuehua Wang, Qizhen Zhuang, Yuan Wu, Junhong Zhang, Yue Lu, Jingjing Wu, Juanjuan Liu, Xiangyu Hu, Ling Han
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