Journal of translational genetics and genomics最新文献

{"title":"The Hong Kong genome project: building genome sequencing capacity and capability for advancing genomic science in Hong Kong","authors":"Annie T. W. Chu, Amy H. Y. Tong, Desiree M. S. Tse, Cario W. S. Lo, Carol C. F. Lau, Cecilia Y. F. Li, Nattily S. Y. Tai, Lap W. Wong, Gigi K. C. Choy, Belinda Y. Y. Tse, Su-vui Lo, Ken Sung, Mullin Yu, None Hong Kong Genome Project, Brian H. Y. Chung","doi":"10.20517/jtgg.2023.22","DOIUrl":"https://doi.org/10.20517/jtgg.2023.22","url":null,"abstract":"Aim: The Hong Kong Genome Project (HKGP) is the first large-scale genome sequencing (GS) project in the Hong Kong Special Administrative Region. The Hong Kong Genome Institute (HKGI) is entrusted with the task of implementing the HKGP. With the aim to sequence 45,000-50,000 genomes in five years, it is the project’s goal to provide participants with more precise diagnosis and personalised treatment, and to drive the application and integration of genomic medicine into routine clinical care. Methods: The HKGI Laboratory’s hardware and software components were customised to tailor to the needs of the project. Sample handling and storage protocol, DNA extraction, and PCR-free GS workflow were developed and optimised. Quality control indicators and metrics for assessing the quality of samples, sequencing libraries and sequencing data were established. Results: The Laboratory is designed to facilitate a unidirectional GS workflow to minimise the risk of contamination. The Sample Manager system handles laboratory data generated from the HKGP samples and biobank. The Laboratory handles and analyses approximately 350-500 samples per week, the majority of which are whole blood. During the first 24 months since the launch of the HKGP, 12,937 participants and their family members (6,680 genomes) have been recruited and sequenced. The sequencing capacity of the Laboratory has been further enhanced to include the latest technologies, such as long-read sequencing and multi-omics in order to meet the target of the HKGP. Conclusion: HKGI Laboratory established a robust GS workflow for the HKGP. The clinical utility of GS will bring precision medicine into routine clinical practice.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136317166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of sodium D, L-3-hydroxybutyrate as adjunct therapy in two siblings with HMG-CoA lyase deficiency","authors":"Beena Devanapalli, Adviye Ayper Tolun, Won-Tae Kim, Tiffany Wotton, Susan Thompson, Shanti Balasubramaniam","doi":"10.20517/jtgg.2023.12","DOIUrl":"https://doi.org/10.20517/jtgg.2023.12","url":null,"abstract":"3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency is a rare autosomal recessive mitochondrial disease characterised by recurrent life-threatening metabolic crises generally presenting in neonates or infancy during catabolic stress triggered by prolonged fasting or intercurrent illness. Acute decompensations with lethargy, vomiting, hypoketotic hypoglycemia and metabolic acidosis may evolve into Reye-like syndrome if untreated, with acute liver failure, hyperammonemic encephalopathy, dilated cardiomyopathy, and death in 20% of cases. Long-term health complications include psychomotor retardation, white matter abnormalities, epilepsy, hepatic steatosis, pancreatitis, cardiomyopathy, and arrythmia. The mitochondrial enzyme catalyses the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, the common final step of ketogenesis and leucine degradation, resulting in diagnostic urinary organic acid pattern (elevated 3-hydroxy-3-methylglutaric, 3-methylgutaconic, 3-methylglutaric, and 3-hydroxyisovaleric acids) with the absence of ketonuria, when deficient. Therapeutic interventions include dietary protein or leucine and fat restriction, carnitine supplementation, avoidance of fasting, and use of carbohydrate-based high caloric intake when unwell. We describe the clinical course and diagnostic work-up in two affected siblings, with the proband presenting with severe neonatal onset disease with metabolic acidosis, non-ketotic hypoglycaemia, hyperammonemia and white matter changes on brain MRI. High-risk screening for a younger sibling led to pre-emptive management with good outcomes. Sodium D, L-3-hydroxybutyrate (S-DL-3OHB) was used in both siblings as an adjunct therapy to prevent cerebral dysfunction and cardiomyopathy, with the rationale that decreased ketogenesis in this disorder may impact the major energy source for the brain and heart during starvation. S-DL-3OHB therapy is a well-tolerated and effective therapeutic option for this disorder.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135304625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kabuki syndrome and rare tumors in a young girl carrying a frameshift kmt2d mutation","authors":"A. Bonuccelli, Tommaso Baldaccini, A. Orsini, E. Alberti, M. Del Pistoia, U. Boggi, B. Toschi, A. Santangelo, E. Randazzo, D. Peroni, Giovanni Federico","doi":"10.20517/jtgg.2022.18","DOIUrl":"https://doi.org/10.20517/jtgg.2022.18","url":null,"abstract":"Kabuki syndrome (KS) is a genetic disorder characterized by typical facial dimorphisms, various degrees of cognitive disability, and congenital anomalies involving the heart, kidneys, gastrointestinal system, and bones. It is accompanied by hypotonia, failure to thrive, obesity, and immunodeficiency. Association with neoplastic lesions has been recently described. We report a 13-year-old girl with KS, an insulinoma, and a benign phyllodes breast tumor with two hepatic lesions: a neuroendocrine tumor metastasis and a ciliated foregut cyst associated with hepatic fibrosis. She had a pilomatrixoma and a junctional melanocytic nevus with cytological atypia. Genetic analysis revealed a heterozygous frameshift variant in the KMT2D gene. Somatic KMT2D variants are in various types of tumors. The role of KMT2D variants in malignancies in KS appears to be related to defective transcription regulation and altered gene expression; however, the mechanism remains unclear. This aims to clarify the relationship between KMT2D gene variants, KS, and susceptibility to neoplastic lesions. For this purpose, a more extensive case series will be needed to accurately describe the patients' neoplastic phenotypes and precise genetic characterization.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45759947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Public and patient involvement in research to support genome services development in the UK","authors":"","doi":"10.20517/jtgg.2022.19","DOIUrl":"https://doi.org/10.20517/jtgg.2022.19","url":null,"abstract":"","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics education for medical specialists: case-based specialty workshops and blended learning","authors":"F. Maher, A. Nisselle, E. Lynch, M. Martyn, Rigan Tytherleigh, Taryn Charles, C. Gaff","doi":"10.20517/jtgg.2023.04","DOIUrl":"https://doi.org/10.20517/jtgg.2023.04","url":null,"abstract":"Aim: To develop and evaluate genomics education programs for health professionals to expedite the translation of genomics into healthcare. Methods: Our co-design team of genetic specialists, expert medical specialist peers, and genomics educators developed two continuing genomics education programs for health professionals: stand-alone, specialty-specific workshops and a generic blended learning course, combining online learning with workshops. Both programs referenced adult learning theories; workshops included case-based learning and expert peer-led discussion. Longitudinal surveys evaluated changes in confidence and understanding of genomic testing processes and clinical practice. Results: We delivered eleven specialty workshops (414 attendees) and a blended learning course comprising four self-directed online modules (61 users) and workshops (71 attendees) for mixed-specialty groups with adult, pediatric, or oncology cases. Surveys (214 workshops; 63 blended) showed that both programs significantly increased confidence and understanding of genomic testing processes. Blended learning participants showed additional gains in confidence after attending a workshop following online learning. Workshop discussions with experts were valued, particularly regarding interpreting and applying results. At follow-up, gains in confidence and understanding were maintained for both programs and 81% of respondents had performed a new genomics activity in clinical practice. Conclusion: Scalable education is needed. Our results suggest that specialty-specific genomics education may not be required to meet the needs of multiple specialties across a health system. Online learning can meet foundational learning needs but may not be sufficient to apply learning to practice. Blended learning offers flexible, continuing education pathways for dispersed national audiences as genomics becomes increasingly used across varied specialties.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics in leukaemia in clinical practice: past, present and the future","authors":"Ho-Ching Leung, A. Leung","doi":"10.20517/jtgg.2023.09","DOIUrl":"https://doi.org/10.20517/jtgg.2023.09","url":null,"abstract":"Acute myeloid leukaemia (AML) is a heterogeneous group of diseases with diverse genetic drivers. The conventional one-size-fits-all approach with chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) has reached an impasse, and only about 40% of patients can achieve long-term survival. Disease heterogeneities have also hampered the development of effective therapy applicable to the multitude of AML subtypes. Recent advances in cancer genetics and genomics have shed light on the genetic underpinnings of AML and both inter-individual and intra-tumoral heterogeneities. These new pieces of knowledge have begun to impact the management and prognostication of AML. They also provide the foundation for personalized treatment for this group of diseases.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic impact of long non-coding RNA lnc-ADAM9 on extracellular matrix pathway in preterm syndrome through down-regulation of mRNA-ADAM9","authors":"Xiaohua Wang, Aiju Liu, D. Hou, Xiaoyan Dong, C. Chu, W. Ju, Junhui Zhang, Yueqi Jia, Xiaoyan Yang, Yunpeng Ji, Tingting Wang, E. Bonney, Gui-Yu Wang, N. Zhong","doi":"10.20517/jtgg.2023.07","DOIUrl":"https://doi.org/10.20517/jtgg.2023.07","url":null,"abstract":"im: Evidence suggests that the risk of spontaneous preterm birth (sPTB) is the result of environmental exposure interacting with genetic risk and is mediated by epigenetic modification. Long non-coding RNA (lncRNA) comprises a large group of regulators of epigenetic modification that has recently become the focus of increased investigation in reproductive science. Human placenta expresses many lncRNAs, and differential expression profiles (DEPs) have identified several lncRNAs as associated with sPTB. However, little is known about lncRNA’s role in the epigenetic modification of the genes potentially involved in sPTB. This study is to better understand the epigenetic regulation of lncRNA on the development of sPTB. Methods: A transcriptomic analysis of human placentas derived from various pregnancy outcomes was performed as a discovery study. This was followed by a quantitative confirmation to validate the differential transcription of lncADAM9, the lncRNA overlapping with the ADAM9 gene locus, and of lncRNA-overlapped mRNA of ADAM9 (mRNA-ADAM9). In vitro examination of lncADAM9 transgenic (TG) HTR8 cells were used to perform functional assessment to address the role of lncADAM9-mediated epigenetic regulation of extracellular matrix-adhesion (ECM-A) associated molecules. This assessment was then expanded to studies of human fetal membranes. Results: We observed that expression of lncADAM9 was increased in sPTB, and this increase was further associated with the down-regulation of mRNA-ADAM9 in human placentas. In vitro, overexpression of lncADAM9 in lncADAM9-transgenic HRT8 cells led to DEPs relevant to ECM-A molecules, particularly at the loci of CNTN1, NRXN2, SPN, ICAM2, and HLA-DPB1. This was also true in fetal membranes from abnormal versus normal fetal membranes. Conclusion: We have studied the epigenetic impact of differentially expressed lncADAM9 on the ECM-A pathway that is associated with sPTB and documented that this impact may be mediated through the down-regulation of mRNA-ADAM9. Our results of demonstrating the epigenetic regulation of lncADAM9 on the ECM-A pathway may help provide greater insight into critical pathogenic mechanisms underlying sPTB.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case with prenatal molecular diagnosis of X-linked transient antenatal Bartter syndrome","authors":"K. Xu, Yanqin Zhang, Xinlin Hou, Hui Yang, Jie Ding, Fang Wang","doi":"10.20517/jtgg.2023.10","DOIUrl":"https://doi.org/10.20517/jtgg.2023.10","url":null,"abstract":"Early-onset polyhydramnios during pregnancy can be caused by X-linked transient antenatal Bartter syndrome. Most of the reported cases were molecularly diagnosed after birth, whereas few cases were diagnosed in the fetus period. We received a pregnant woman who had polyhydramnios detected by ultrasound imaging at 25 weeks of gestation, and treated with magnesium sulfate, indomethacin and an amnioreduction at 30 weeks of gestation, whereas amniotic fluid decreased spontaneously since 32 weeks of gestation. Prenatal molecular testing showed the fetus carried MAGED2 hemizygous variant c.967C>T [p. (Asp323*)] inherited from the mother. The preterm boy did not present with polyuria and electrolytes and acid-base imbalance in the early neonatal period, and had good development without polyuria at the age of 20 months. We presented the phenotypes of a Chinese case with a prenatal diagnosis of X-linked transient antenatal Bartter syndrome and his response to prenatal indomethacin treatment. Early identification of the condition helps to provide appropriate prenatal genetic counseling and postnatal management.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity associated cancers, genetics, epigenetics and elephants.","authors":"Nathan A Berger","doi":"10.20517/jtgg.2023.23","DOIUrl":"https://doi.org/10.20517/jtgg.2023.23","url":null,"abstract":"","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10588055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marketing and publicity strategies for launching the pilot phase of the Hong Kong Genome Project","authors":"","doi":"10.20517/jtgg.2023.01","DOIUrl":"https://doi.org/10.20517/jtgg.2023.01","url":null,"abstract":"","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}