Molecular Genetics & Genomic Medicine最新文献

{"title":"Performance of Dysmorphology-Based Screening for Genetic Disorders in Pediatric Congenital Heart Disease Supports Wider Genetic Testing.","authors":"Benjamin M Helm, Lindsey R Helvaty, Erin Conboy, Gabrielle C Geddes, Brett H Graham, Melissa Lah, Leah Wetherill, Benjamin J Landis, Stephanie M Ware","doi":"10.1002/mgg3.70040","DOIUrl":"10.1002/mgg3.70040","url":null,"abstract":"<p><strong>Background: </strong>Dysmorphology evaluation is important for congenital heart disease (CHD) assessment, but there are no prior investigations quantifying the screening performance compared to standardized genetics evaluations. We investigated this through systematic dysmorphology assessment in CHD patients with standardized genetic testing in primarily pediatric patients with CHD.</p><p><strong>Methods: </strong>Dysmorphology evaluations preceding genetic testing results allowed us to test for associations between dysmorphic status and genetic diagnoses while adjusting for extracardiac anomalies (ECAs). We use a test-negative case-control design on a pediatric inpatient CHD cohort for our study.</p><p><strong>Results: </strong>Of 568 patients, nearly 96% of patients completed genetic testing, primarily chromosome microarray (CMA) ± exome sequencing-based genetic testing (493/568, 86.8%). Overall, 115 patients (20.2%) were found to have genetic diagnoses, and dysmorphic patients had doubled risk of genetic diagnoses, after ECA adjustment (OR = 2.10, p = 0.0030). We found that 7.9% (14/178) of ECA-/nondysmorphic patients had genetic diagnoses, which increased to 13.5% (26/192) in the ECA-/dysmorphic patients. Nearly 43% of ECA+/dysmorphic patients had genetic diagnoses (63/147). The positive predictive value of dysmorphic status was only 26.3%, and the negative predictive value of nondysmorphic status was 88.7%.</p><p><strong>Conclusions: </strong>Dysmorphology-based prediction of genetic disorders is limited because of diagnoses found in apparently isolated CHD. Our findings represent one of the only assessments of phenotype-based screening for genetic disorders in CHD and should inform clinical genetics evaluation practices for pediatric CHD.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70040"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11588853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716553","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":"Parkinson's Disease Polygenic Risk Score and Neurological Involvement in Carriers of the FMR1 Premutation Allele: A Case for Genetic Modifier.","authors":"Danuta Z Loesch, Freddy Chafota, Minh Q Bui, Elsdon Storey, Anna Atkinson, Nicholas G Martin, Scott D Gordon, Miguel E Rentería, Randi J Hagerman, Flora Tassone","doi":"10.1002/mgg3.70043","DOIUrl":"10.1002/mgg3.70043","url":null,"abstract":"<p><strong>Background: </strong>Premutation alleles of the FMR1 X-linked gene containing CGG repeat expansions ranging from 55 to 200 are associated with diverse late-onset neurological involvements, including most severe disorder termed Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). It is intriguing that at least one-third of male, and a much lower than predicted from the X-linkage proportion of female carriers are free of this syndrome. This suggests the existence of secondary genetic factors modifying the risk of neurological involvements in these carriers. Considering the occasional presence of parkinsonian features in FXTAS, we explored the possibility that the Parkinson's Disease Polygenic Risk Score (PD PRS) is related to the occurrence of FXTAS or less severe neurological involvements, in premutation carriers.</p><p><strong>Methods: </strong>The Genome-wide SNP genotyping and clinical data on neurological status were obtained from 250 unrelated affected and non-affected male and female adult carriers of the premutation. The medians for the Parkinson's Disease Polygenic Risk Score (PD PRS) were compared between the groups of asymptomatic and neurologically affected carriers, and the association of PD PRS with neurological involvement in context with the other known risk factors was explored by fitting univariate and multiple logistic regression models.</p><p><strong>Results: </strong>There was a significant difference between the medians from the asymptomatic versus neurologically affected (FXTAS+) groups (p = 0.009). The FXTAS+ status was significantly associated with age at testing (p < 0.001), gender (p = 0.026), and with PD PRS (p = 0.021). The contribution of PD PRS remained significant after adjusting for age and gender (p = 0.044).</p><p><strong>Conclusions: </strong>We have obtained the first evidence for the relationship between PD PRS and the risk of FXTAS or lesser neurological involvements in the FMR1 premutation carriers. This suggests the role of Parkinson's disease polygenic variants as genetic modifiers of the risk of late onset neurological changes in these carriers.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70043"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716608","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":"Development of a Tagmentation-Based Next-Generation Sequencing Clinical Assay as an Alternative to Capillary Electrophoresis-Based Sequencing.","authors":"Wei Cheng David Kuek, Chean Nee Chai, Wei Ming Jason Tham, Alvin Yu Jin Ng, Dilys Shi Ning Lau, Janice Yen Qi Loo, Dan Thu Van, Joanna Kia Min Tan, Chun Kiat Lee, Benedict Yan, Tim Hon Man Chan","doi":"10.1002/mgg3.70035","DOIUrl":"10.1002/mgg3.70035","url":null,"abstract":"<p><strong>Background: </strong>Next-generation sequencing (NGS) technology enables sample multiplexing for interrogation of multiple regions of interest (ROI). Leveraging this, together with access to affordable NGS platforms, we explored the practicality of moving capillary electrophoresis (CE), noncapillary electrophoresis and single-gene testing to NGS. In this work, we evaluated the iSeq 100's capacity to validate 89 samples at once.</p><p><strong>Methods: </strong>Genomic DNA was extracted from 89 archival samples of varying specimen types. Polymerase chain reaction (PCR) was done with in house primers, library preparation with the Nextera XT Library Preparation Kit and cleaning up with paramagnetic beads. The sequencing was performed on one Illumina iSeq 100 flow cell.</p><p><strong>Results: </strong>With our workflow, 88 out of 89 samples were accurately sequenced with variant alleles identified. One sample of the 88 samples was initially discordant because the primers used were in a heterozygous deletion region. Upon redesigning of primers, the sample proved concordant.</p><p><strong>Conclusions: </strong>The iSeq-Nextera workflow proved accurate. However, variant allele frequencys generated by the Nextera are not precise.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70035"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668095","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":"Reclassification of Two MLH1 Variants of Uncertain Significance Utilizing Clinical and Functional Data.","authors":"Jane Hübertz Frederiksen, Ulf Birkedal, Sarah Bachmann, Elisabeth Victoria Eliesen, Lene Juel Rasmussen, Katja Venborg Pedersen, Lana Al-Zehhawi, Susanne E Boonen, Lotte Krogh, Karina Rønlund, Lise Graversen, Jannie Assenholt, Kjeld Schmiegelow, Karin Wadt, Anne-Marie Gerdes, Thomas V O Hansen","doi":"10.1002/mgg3.70026","DOIUrl":"10.1002/mgg3.70026","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic variants in the mismatch repair genes are associated with an elevated lifetime risk of colorectal cancer (CRC). We previously identified two variants of uncertain significance (VUS) in the MLH1 gene, c.696_698del, p.(Cys233del) and c.1919C > G, p.(Pro640Arg), in Danish families with numerous occurrences of CRC.</p><p><strong>Methods: </strong>To reclassify the variants we collected clinical data, initiated tumor and co-segregation analysis, and performed RNA splicing analysis, subcellular localization, and protein stability studies.</p><p><strong>Results: </strong>The functional analysis revealed that the c.696_698del, p.(Cys233del) variant had an effect at the RNA level, on subcellular localization, and on protein stability, while the c.1919C > G, p.(Pro640Arg) variant showed decreased expression in localization studies and decreased protein stability. These results suggest both variants disrupt DNA mismatch repair.</p><p><strong>Conclusion: </strong>By applying all collected data and functional results we propose to reclassify the c.696_698del, p.(Cys233del) and the c.1919C > G, p.(Pro640Arg) variants as likely pathogenic (class 4) using MMR gene-specific ACMG/AMP guidelines. Consequently, the two MLH1 variants can now be used for risk assessment of variant carriers, while family members without the variants can be excluded from intensified cancer surveillance and follow population recommendations.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70026"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639349","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 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}