European journal of medical genetics最新文献

{"title":"New description of an MRPS2 homozygous patient: Further features to help expend the phenotype","authors":"Thalia Papadopoulos ,&nbsp;Pauline Gaignard ,&nbsp;Manuel Schiff ,&nbsp;Marlène Rio ,&nbsp;Daniela Karall ,&nbsp;Adrien Legendre ,&nbsp;Alain Verloes ,&nbsp;Lyse Ruaud","doi":"10.1016/j.ejmg.2023.104889","DOIUrl":"10.1016/j.ejmg.2023.104889","url":null,"abstract":"<div><p><span><span>Mutated mito-ribosomal protein S2 (MRPS2) was already described in only three subjects, two with sensorineural hearing impairment, mild developmental delay, hypoglycemia, lactic acidemia and combined </span>oxidative phosphorylation system deficiency and another, recently, presenting with a less severe phenotype. In order to expand the phenotype, we describe a new </span><em>MRPS2</em><span> homozygous subject who shows particular features which have not yet been reported: initial microcephaly<span>, joint hypermobility and autistic features.</span></span></p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458743","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}

{"title":"Early-onset diabetes in Africa: A mini-review of the current genetic profile","authors":"Samuel Mawuli Adadey ,&nbsp;Joy Afua Mensah ,&nbsp;Kojo Sekyi Acquah ,&nbsp;James Abugri ,&nbsp;Richard Osei-Yeboah","doi":"10.1016/j.ejmg.2023.104887","DOIUrl":"10.1016/j.ejmg.2023.104887","url":null,"abstract":"<div><p><span><span>Early-onset diabetes is poorly diagnosed partly due to its heterogeneity and variable presentations. Although several genes have been associated with the disease, these genes are not well studied in Africa. We sought to identify the major neonatal, early childhood, juvenile, or early-onset diabetes genes in Africa; and evaluate the available molecular methods used for investigating these gene variants. A literature search was conducted on PubMed, </span>Scopus<span>, Africa-Wide Information, and Web of Science databases. The retrieved records were screened and analyzed to identify genetic variants associated with early-onset diabetes. Although 319 records were retrieved, 32 were considered for the current review. Most of these records (22/32) were from North Africa. The disease condition was genetically heterogenous with most cases possessing unique gene variants. We identified 22 genes associated with early-onset diabetes, 9 of which had variants (n = 19) classified as pathogenic or likely pathogenic (PLP). Among the PLP variants, </span></span><em>IER3IP1</em><span>: p.(Leu78Pro) was the variant with the highest number of cases. There was limited data from West Africa, hence the contribution of genetic variability to early-onset diabetes in Africa could not be comprehensively evaluated. It is worth mentioning that most studies were focused on natural products as antidiabetics and only a few studies reported on the genetics of the disease. </span><span><em>ABCC8</em></span> and <em>KCNJ11</em><span><span> were implicated as major contributors to early-onset diabetes gene networks. Gene ontology analysis of the network associated ion channels, </span>impaired glucose tolerance<span>, and decreased insulin secretions to the disease. Our review highlights 9 genes from which PLP variants have been identified and can be considered for the development of an African diagnostic panel. There is a gap in early-onset diabetes genetic research from sub-Saharan Africa which is much needed to develop a comprehensive, efficient, and cost-effective genetic panel that will be useful in clinical practice on the continent and among the African diasporas</span></span><strong>.</strong></p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298762","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}

{"title":"Resolving fetal hydrops – A rare entity","authors":"Deepti Saxena ,&nbsp;Amit K. Tiwari ,&nbsp;Rameshwar Prasad ,&nbsp;Saumya Srivastav","doi":"10.1016/j.ejmg.2023.104888","DOIUrl":"10.1016/j.ejmg.2023.104888","url":null,"abstract":"<div><p><span><span>Non-immune hydrops fetalis<span> (NIHF) is abnormal accumulation of serous fluid in ≥2 interstitial spaces with no evidence of maternal red cell </span></span>alloimmunization. Leaving a few treatable conditions, it is generally considered as a sign of poor fetal outcome. Bi-allelic variants in </span><em>THSD1</em><span> have been found to be to be associated with phenotypes ranging from lethal NIHF to persistent edema. Here, we report a family with non-immune hydrops in two successive pregnancies. Whole exome sequencing in second pregnancy identified a homozygous truncating variant in </span><em>THSD1</em> (NM_018676:c.892G&gt;T:p.Glu298Ter). Postnatal follow up showed gradual resolution of the accumulated fluid and normal development. This report further strengthens the association of variants in <em>THSD1</em> with NIHF.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294960","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}

{"title":"Cardiovascular involvement in later-onset malonyl-CoA decarboxylase deficiency: Case studies and literature review","authors":"Emanuele Monda ,&nbsp;Athanasios Bakalakos ,&nbsp;Petros Syrris ,&nbsp;Saidi Mohiddin ,&nbsp;Sacha Ferdinandusse ,&nbsp;Elaine Murphy ,&nbsp;Perry Mark Elliott","doi":"10.1016/j.ejmg.2023.104885","DOIUrl":"10.1016/j.ejmg.2023.104885","url":null,"abstract":"<div><h3>Background</h3><p>Malonyl-CoA decarboxylase deficiency (MLYCDD) is an ultra-rare inherited metabolic disorder<span>, characterized by multi-organ involvement manifesting during the first few months of life. Our aim was to describe the clinical, biochemical, and genetic characteristics of patients with later-onset MLYCDD.</span></p></div><div><h3>Methods</h3><p><span>Clinical and biochemical characteristics of two patients aged 48 and 29 years with a confirmed molecular diagnosis of MLYCDD were examined. A </span>systematic review of published studies describing the characteristics of cardiovascular involvement of patients with MLYCDD was performed.</p></div><div><h3>Results</h3><p><span>Two patients diagnosed with MLYCDD during adulthood were identified. The first presented with hypertrophic cardiomyopathy<span> and ventricular pre-excitation and the second with dilated cardiomyopathy (DCM) and mild-to-moderate left ventricular (LV) systolic dysfunction. No other clinical manifestation typical of MLYCDD was observed. Both patients showed slight increase in malonylcarnitine in their plasma acylcarnitine profile, and a reduction in malonyl-CoA decarboxylase activity. During follow-up, no deterioration of LV </span></span>systolic function was observed.</p><p>The systematic review identified 33 individuals with a genetic diagnosis of MLYCDD (median age 6 months [IQR 1–12], 22 males [67%]). Cardiovascular involvement was observed in 64% of cases, with DCM the most common phenotype. A modified diet combined with levocarnitine supplementation resulted in the improvement of LV systolic function in most cases. After a median follow-up of 8 months, 3 patients died (two heart failure-related and one arrhythmic death).</p></div><div><h3>Conclusions</h3><p>For the first time this study describes a later-onset phenotype of MLYCDD patients, characterized by single-organ involvement, mildly reduced enzyme activity, and a benign clinical course.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138046660","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}

{"title":"Response to the comment on Diderich et al. “The role of a multidisciplinary team in managing variants of uncertain clinical significance in prenatal genetic diagnosis” (EJMG 66(10),104844)","authors":"Karin E.M. Diderich,&nbsp;Jasmijn E. Klapwijk,&nbsp;Vyne van der Schoot,&nbsp;Myrthe van den Born,&nbsp;Martina Wilke,&nbsp;Marieke Joosten,&nbsp;Kyra E. Stuurman,&nbsp;Lies H. Hoefsloot,&nbsp;Diane Van Opstal,&nbsp;Hennie T. Brüggenwirth,&nbsp;Malgorzata I. Srebniak","doi":"10.1016/j.ejmg.2023.104884","DOIUrl":"https://doi.org/10.1016/j.ejmg.2023.104884","url":null,"abstract":"","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223001908/pdfft?md5=125a1163205c3026ea6b7faaa4f1b8ee&pid=1-s2.0-S1769721223001908-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134688795","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":"National clinical Genetic Networks - GENets - Establishment of expert collaborations in Denmark","authors":"Dorte L. Lildballe ,&nbsp;Anja Lisbeth Frederiksen ,&nbsp;Bitten Schönewolf-Greulich ,&nbsp;Charlotte Brasch-Andersen ,&nbsp;Charlotte Kvist Lautrup ,&nbsp;Helena Gásdal Karstensen ,&nbsp;Inge Søkilde Pedersen ,&nbsp;Lone Sunde ,&nbsp;Lotte Risom ,&nbsp;Maria Rasmussen ,&nbsp;Mette Bertelsen ,&nbsp;Mette Klarskov Andersen ,&nbsp;Nanna Dahl Rendtorff ,&nbsp;Pernille Axél Gregersen ,&nbsp;Pernille M. Tørring ,&nbsp;Sophia Hammer-Hansen ,&nbsp;Susanne E. Boonen ,&nbsp;Suzanne Granhøj Lindquist ,&nbsp;Trine Bjørg Hammer ,&nbsp;Birgitte R. Diness","doi":"10.1016/j.ejmg.2023.104872","DOIUrl":"10.1016/j.ejmg.2023.104872","url":null,"abstract":"<div><p><span>Genetic<span> conditions are often familial, but not all relatives receive counseling from the same institution. It is therefore necessary to ensure consistency in variant interpretation, counseling practices, and clinical follow up across health care providers. Furthermore, as new possibilities for gene-specific treatments emerge and </span></span>whole genome sequencing becomes more widely available, efficient data handling and knowledge sharing between clinical laboratory geneticists and medical specialists in clinical genetics are increasingly important.</p><p>In Denmark, these needs have been addressed through the establishment of collaborative national networks called Genetic Expert Networks or \"GENets\". These networks have enhanced patient and family care significantly by bringing together groups of experts in national collaborations. This promotes coordinated clinical care, the dissemination of best clinical practices, and facilitates the exchange of new knowledge.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648721","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}

{"title":"Letter to the Editor: Comment to Diderich et al. “The role of a multidisciplinary team in managing variants of uncertain clinical significance in prenatal genetic diagnosis” (EJMG 66(10),104844)","authors":"Fang Chen,&nbsp;Dong-Zhi Li","doi":"10.1016/j.ejmg.2023.104883","DOIUrl":"10.1016/j.ejmg.2023.104883","url":null,"abstract":"","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223001891/pdfft?md5=12bd5078f3e5011e6b4e685549cdac9a&pid=1-s2.0-S1769721223001891-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013961","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 evaluation of variants of uncertain significance at exon-intron junction by splicing assay in patients with Mowat–Wilson syndrome","authors":"Yasuyo Suzuki ,&nbsp;Noriko Nomura ,&nbsp;Kenichiro Yamada ,&nbsp;Yasukazu Yamada ,&nbsp;Ayumi Fukuda ,&nbsp;Kyoko Hoshino ,&nbsp;Shinpei Abe ,&nbsp;Kenji Kurosawa ,&nbsp;Mie Inaba ,&nbsp;Seiji Mizuno ,&nbsp;Nobuaki Wakamatsu ,&nbsp;Shin Hayashi","doi":"10.1016/j.ejmg.2023.104882","DOIUrl":"10.1016/j.ejmg.2023.104882","url":null,"abstract":"<div><p>High-throughput sequencing has identified vast numbers of variants in genetic disorders. However, the significance of variants at the exon-intron junction remains controversial. Even though most cases of Mowat–Wilson syndrome (MOWS) are caused by heterozygous loss-of-function variants in <span><em>ZEB2</em></span>, the pathogenicity of variants at exon-intron junction is often indeterminable. We identified four intronic variants in 5/173 patients with clinical suspicion for MOWS, and evaluated their pathogenicity by <em>in vitro</em><span><span><span><span> analyses. The minigene analysis showed that c.73+2T&gt;G caused most of the transcripts </span>skipping exon 2, while c.916+6T&gt;G led to partial skipping of exon 7. No splicing abnormalities were detected in both c.917-21T&gt;C and c.3067+6A&gt;T. The minigene analysis reproduced the splicing observed in the blood cells of the patient with c.73+2T&gt;G. The degree of the exon skipping was concordant with the severity of MOWS; while the patient with c.73+2T&gt;G was typical MOWS, the patient with c.916+6T&gt;G showed milder phenotype which has been seldom reported. Our results demonstrate that </span>mRNA splicing assays using the minigenes are valuable for determining the </span>clinical significance<span> of intronic variants in patients with not only MOWS but also other genetic diseases with splicing aberrations and may explain atypical or milder cases, such as the current patient.</span></span></p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013962","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}

{"title":"Serum alkaline phosphatase can be elevated in patients with hypophosphatasia due to liver disease","authors":"Evert F.S. van Velsen ,&nbsp;Zografia Zervou ,&nbsp;M. Carola Zillikens","doi":"10.1016/j.ejmg.2023.104866","DOIUrl":"10.1016/j.ejmg.2023.104866","url":null,"abstract":"<div><h3>Background</h3><p>Hypophosphatasia (HPP) is a rare inherited disorder caused by pathogenic loss-of-function variants in the <em>ALPL</em> gene, encoding the tissue-nonspecific isoenzym of alkaline phosphatase (ALP; TNSALP). Low serum ALP is the biochemical hallmark of HPP, but it is unknown whether ALP levels can increase due to concurring liver disease, which may lead to a missed diagnose of HPP. We present a patient with genetically confirmed HPP, who showed a transient increase of serum ALP levels due to alcohol-induced hepatitis.</p></div><div><h3>Clinical report</h3><p>A 71-year old man was seen at our Bone Center for surveillance of HPP. Serum ALP was always low (23 U/L; reference value: &lt;115 U/L). During follow-up, his serum ALP increased (156 U/L, further rising to 204 U/L), with concomitantly elevated serum gamma-glutamyl transferase and transaminases, and a rise in bone specific ALP (18.7 μg/L; reference value: 5.7–32.9 μg/L). This was attributed to alcohol-induced hepatitis. After refraining from alcohol intake, both serum ALP and bone specific ALP levels returned to initial low levels (30 U/L and 4.3 μg/L respectively).</p></div><div><h3>Conclusions</h3><p>We demonstrated the history of a 71-year old patient with HPP, presenting during routine follow-up with an elevated serum ALP level up to 204 U/L due to alcohol-induced hepatitis. This case illustrates that the diagnosis of HPP can potentially be missed when ALP levels are normal or elevated due to a concomitant liver disease.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223001726/pdfft?md5=5748b05eaf84bf785fb3f9c5e38be949&pid=1-s2.0-S1769721223001726-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233454","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":"Data collection on rare bone and mineral conditions in Europe: The landscape of registries and databases","authors":"Ana Luisa Priego Zurita ,&nbsp;Corinna Grasemann ,&nbsp;Manila Boarini ,&nbsp;Roland Chapurlat ,&nbsp;Marina Mordenti ,&nbsp;ERN BOND Working Group 5 ,&nbsp;Muhammad Kassim Javaid ,&nbsp;Natasha M. Appelman-Dijkstra","doi":"10.1016/j.ejmg.2023.104868","DOIUrl":"https://doi.org/10.1016/j.ejmg.2023.104868","url":null,"abstract":"<div><h3>Background</h3><p>knowledge on the natural history of rare diseases is necessary to improve outcomes. Disease registries may play a key role in covering these unmet needs in the rare bone and mineral community.</p></div><div><h3>Objective</h3><p>to map existing bone and mineral conditions registries in Europe and their characteristics.</p></div><div><h3>Methods</h3><p>online survey about the use of registries/databases and their characteristics. This survey was disseminated among members of the European Reference Network on Rare Bone Diseases (ERN BOND) and non-ERN experts in the field of bone and mineral conditions as well as patient organisations.</p></div><div><h3>Results</h3><p>sixty-three responses from health care providers (HCPs) and 10 responses from patient groups (PGs) were collected. The response rate for ERN BOND members was 55%. Of 63 HCPs, 37 declared using a registry. Osteogenesis imperfecta (OI) was the most registered condition. We mapped 3 international registries, all were disease-specific.</p></div><div><h3>Conclusions</h3><p>There is a need for developing a common high-quality platform for registering rare bone and mineral conditions.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S176972122300174X/pdfft?md5=b419f9d5f02b5b39de01c40e247713d4&pid=1-s2.0-S176972122300174X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92123774","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}