Human Heredity最新文献

{"title":"A Comprehensive Study of Disease-Causing Variants in PAH, QDPR, PTS, and PCD Genes in Iranian Patients with Hyperphenylalaninemia: A Systematic Review.","authors":"Mahmoud Ghanei, Seyedeh Helia Sadat Fatemi, Tayebeh Hamzehlouei","doi":"10.1159/000529037","DOIUrl":"10.1159/000529037","url":null,"abstract":"<p><strong>Background: </strong>Hyperphenylalaninemia (HPA) is an autosomal recessive disorder that results from a deficiency in the phenylalanine hydroxylase enzyme (PAH) or from a flaw in the genes that are responsible for the biosynthesis or regeneration of the cofactor tetrahydrobiopterin (BH4), including GCH1, SR, QDPR, PTS, and PCD. Identification of disease-causing variants in these genes can help physicians and clinical geneticists in differential diagnosis, appropriate prescription drugs, and saving time and cost. This study attempted to identify these genes' most prevalent disease-causing variants in Iranian HPA patients.</p><p><strong>Summary: </strong>This study was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Before it started, the flow work and inclusion/exclusion criteria were published as a protocol in PROSPERO (CRD42021273705). We conducted a comprehensive search on December 10, 2022, on international online databases, including Web of Science, Scopus, EMBASE, Science Direct, PubMed/Medline, Google Scholar, SID, ISC, and Magiran search engine, to find pertinent publications. Some studies were chosen based on inclusion and exclusion criteria. Altogether, 1,243 Iranian patients from 13 articles were considered. In total, we identified 129 distinct disease-causing variants in PAH (20 novel variants), 29 in QDPR (17 novel variants), 15 in PTS (seven novel variants), and one novel variant in PCD. Twenty disease-causing variants for PAH, 18 for QDPR, and 8 for PTS are included in the genes' proposed genetic diagnostic panels. These panels include more than 75% of the documented disease-causing variants in the Iranian population.</p><p><strong>Key messages: </strong>The findings of this research illustrated the spectrum of disease-causing variants in the PAH, QDPR, PTS, and PCD genes identified in Iranian HPA patients. Common disease-causing variants of these genes may be chosen as a preliminary diagnostic panel for early diagnosis and lowering therapy costs.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":"8-17"},"PeriodicalIF":1.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10750328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10527867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Violation of the constant genetic effect assumption can result in biased estimates for non-linear Mendelian randomization","authors":"S. Burgess","doi":"10.1101/2022.10.26.22280570","DOIUrl":"https://doi.org/10.1101/2022.10.26.22280570","url":null,"abstract":"Non-linear Mendelian randomization is an extension of conventional Mendelian randomization that performs separate instrumental variable analyses in strata of the study population with different average levels of the exposure. The approach estimates a localized average causal effect function, representing the average causal effect of the exposure on the outcome at different levels of the exposure. The commonly-used residual method for dividing the population into strata works under the assumption that the effect of the genetic instrument on the exposure is linear and constant in the study population. However, this assumption may not hold in practice. We use the recently developed doubly-ranked method to re-analyse various datasets previously analysed using the residual method. In particular, we consider a genetic score for 25-hydroxyvitamin D [25(OH)D] used in a recent non-linear Mendelian randomization analysis to assess the potential effect of vitamin D supplementation on all-cause mortality. We show that the effect of the genetic score on 25(OH)D concentrations varies strongly, with a five-fold difference in the estimated genetic association with the exposure in the lowest and highest decile groups. Evidence for a protective causal effect of vitamin D supplementation on all-cause mortality in low vitamin D individuals is evident for the residual method, but not for the doubly-ranked method. We show that the constant genetic effect assumption is more reasonable for some exposures, and less reasonable for others. If the doubly-ranked method indicates that this assumption is violated, then estimates from both the residual and doubly-ranked methods can be biased, although bias was smaller on average in the doubly-ranked method. Analysts should compare results from both methods, as well as considering transforming the exposure to reduce heterogeneity in the genetic effect on the exposure.","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":"1 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41898686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel mutation in patients with type A insulin resistance syndrome.","authors":"Liling Zhao, Hongmei Dai, Qin Zhang, Wenmu Hu, Ping Jin","doi":"10.1159/000525223","DOIUrl":"10.1159/000525223","url":null,"abstract":"<p><strong>Introduction: </strong>Type A insulin resistance syndrome is a rare type of congenital insulin resistance often caused by heterozygous mutations in the insulin receptor gene (INSR). The aim of this study is to explore the clinical and genetic characteristics of three patients with type A insulin resistance syndrome from two Chinese families.</p><p><strong>Methods: </strong>The peripheral blood samples were collected from each family members. Whole-exome sequencing were performed on three patients.</p><p><strong>Results: </strong>Patient #1 was diagnosed with hyperinsulinemia at the age of 11 years and presented with hirsutism, acanthosis nigricans, and polycystic ovaries by 13 years. A heterozygous c.3470A > G mutation in the INSR gene was identified in patient #1. Patient #2 was a 13-year-old girl who presented with insulin resistance, polycystic ovary, and hyperandrogenemia. A novel c.3601C > G INSR mutation was identified in patient #2. Co-segregated analysis showed that the c.3601C > G mutation was also found in her father, who had hyperinsulinemia and diabetes mellitus, which was consistent with autosomal dominant inheritance. SIFT and PolyPhen-2 predicted that the c.3470A > G and c.3601C > G mutations in INSR had damaging effects.</p><p><strong>Conclusion: </strong>Our study expands the genotypic and phenotypic spectrum of type A insulin resistance syndrome. Awareness of the clinical features coupled with INSR gene screening is key to early detection and active intervention.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":"87 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43136904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mitochondrial tRNAAsp T7561C, tRNAHis C12153T and A12172G mutations may be associated with essential hypertension in a Han Chinese pedigree.","authors":"Haiying Fu, Jinming Sun, Xiaoyan Xu","doi":"10.1159/000524163","DOIUrl":"10.1159/000524163","url":null,"abstract":"<p><strong>Objectives: </strong>Mutations in mitochondrial tRNA (mt-tRNA) are the important causes for maternally inherited hypertension, however, the pathophysiology of mt-tRNA mutations in clinical expression of hypertension remains poorly understood.</p><p><strong>Material and methods: </strong>In this study, we report the molecular features of a Han Chinese pedigree with maternally transmitted essential hypertension. The entire mitochondrial genomes are PCR amplified and sequenced, Moreover, phylogenetic analysis, haplogroup analysis, as well as pathogenicity scoring system are used to assess the potential roles for mtDNA mutations.</p><p><strong>Results: </strong>Strikingly, among ten matrilineal relatives, three of them suffer from variable degree of hypertension at different age at onset. Sequence analysis of the complete mitochondrial genomes suggests the presence of three possible pathogenic mtDNA mutations: tRNAAsp T7561C, tRNAHis C12153T and A12172G, together with a set of variants belonging to East Asian mitochondrial haplogroup M7a. Interestingly, the T7561C mutation occurs at position 44 in the variable region of tRNAAsp, while the C12153T and A12172G mutations are localized at extremely conserved nucleotides in the D-arm and anticodon stem of tRNAHis gene, respectively, which are critical for tRNA steady-state level and function.</p><p><strong>Conclusions: </strong>Mitochondrial T7561C, C12153T and A12172G mutations may lead to the failure in tRNAs metabolism, and cause mitochondrial dysfunction that is responsible for hypertension. However, the homoplasmy form of mt-tRNA mutations, incomplete penetrance of hypertension suggest that T7561C, C12153T and A12172G mutations are insufficient to produce the clinical phenotype, hence, other risk factors such as environmental factors, nuclear genes and epigenetic modifications may contribute to the phenotypic manifestation of maternally inherited hypertension in this Chinese pedigree.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":"87 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49367155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts.","authors":"Rasha N Alotaibi, Brian J Howe, Lina M Moreno Uribe, Carla Sanchez, Frederic W B Deleyiannis, Carmencita Padilla, Fernando A Poletta, Ieda M Orioli, Carmen J Buxó, George L Wehby, Alexandre R Vieira, Jeffrey Murray, Consuelo Valencia-Ramírez, Claudia P Restrepo Muñeton, Ross E Long, John R Shaffer, Steven E Reis, Seth M Weinberg, Katherine Neiswanger, Daniel W McNeil, Mary L Marazita","doi":"10.1159/000522642","DOIUrl":"10.1159/000522642","url":null,"abstract":"<p><p>Enamel hypoplasia causes reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. A genome-wide association of enamel hypoplasia was performed in multiple cohorts, overall comprising 7,159 individuals ranging in age from 7-82 years. Mixed-models were used to test for genetic association while simultaneously accounting for relatedness and genetic population structure. Meta-analysis was then performed. More than 5 million single-nucleotide polymorphisms were tested in individual cohorts. Analyses of the individual cohorts and meta-analysis identified association signals close to genome-wide significance (P < 510-8), and many suggestive association signals (510-8 < P < 510-6) near genes with plausible roles in tooth/enamel development. The strongest association signal (P = 1.5710-9) was observed near BMP2K in one of the individual cohorts. Additional suggestive signals were observed near genes with plausible roles in tooth development in the meta-analysis, such as SLC4A4 which can influence enamel hypoplasia. Additional human genetic studies are needed to replicate these results and functional studies in model systems are needed to validate our findings.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9284765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"50th European Mathematical Genetics Meeting (EMGM) 2022.","authors":"Jennifer Asimit","doi":"10.1159/000524615","DOIUrl":"10.1159/000524615","url":null,"abstract":"","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":"Vol. 1","pages":"1-42"},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48742097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front & Back Matter","authors":"G. Dahlberg","doi":"10.1159/000521474","DOIUrl":"https://doi.org/10.1159/000521474","url":null,"abstract":"","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":"86 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43991123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front & Back Matter","authors":"G. Dahlberg","doi":"10.1159/000518555","DOIUrl":"https://doi.org/10.1159/000518555","url":null,"abstract":"","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":"85 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48080807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front & Back Matter","authors":"","doi":"10.1159/000517133","DOIUrl":"https://doi.org/10.1159/000517133","url":null,"abstract":"69 49th European Mathematical Genetics Meeting (EMGM) 2021 Génin, E. (Brest) Cover illustration © iStock.com know what matters in karger.com/genetics Genetics K I2 01 67 _g en et ic s_ 28 0 IA 21 03 6_ 21 0x 28 0 Practical e-learning on setting up genetic testing in European hospitals Can my hospital benefi t from next-generation sequencing? This free-to-access, e-learning course has been created for hospital directors and medical managers of European hospitals wishing to improve their genetic testing. It has been compiled by a multidisciplinary team of expert authors from pathology, health economics, and bioinformatics. Students will leave with a solid understanding of the benefi ts of genetic testing, and the practical implications of setting up either an in-house laboratory or outsourced analyses. Authors: Fernando Schmitt; Rhodri Saunders; Stefan Nicolet FREE ENROLLMENT!","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":"1 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47664059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front & Back Matter","authors":"G. Dahlberg","doi":"10.1159/000515579","DOIUrl":"https://doi.org/10.1159/000515579","url":null,"abstract":"","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48716703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}