Article
Biochemistry & Molecular Biology
Lucia Pia Bruno, Gabriella Doddato, Floriana Valentino, Margherita Baldassarri, Rossella Tita, Chiara Fallerini, Mirella Bruttini, Caterina Lo Rizzo, Maria Antonietta Mencarelli, Francesca Mari, Anna Maria Pinto, Francesca Fava, Alessandra Fabbiani, Vittoria Lamacchia, Anna Carrer, Valentina Caputo, Stefania Granata, Elisa Benetti, Kristina Zguro, Simone Furini, Alessandra Renieri, Francesca Ariani
Summary: Intelectual disability (ID) and autism spectrum disorder (ASD) are often associated and characterized by impairments in cognitive processes and daily life tasks. Molecular diagnosis is crucial for improving prognosis and initiating treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Jingjing Xiang, Yang Ding, Fei Yang, Ang Gao, Wei Zhang, Hui Tang, Jun Mao, Quanze He, Qin Zhang, Ting Wang
Summary: This study aimed to identify genetic causes of developmental delay and/or intellectual disability in 17 children using whole-exome sequencing and exome-based copy number variation analysis. The overall diagnostic rate was 58.8%, with diagnostic SNVs/Indels accounting for 41.2% and diagnostic CNVs accounting for 17.6%. These findings expand the mutation spectrum of genes related to DD/ID and suggest that exome-based CNV analysis could improve diagnostic yield.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Maria Asif, Maryam Anayat, Faiza Tariq, Tanzeela Noureen, Ghulam Naseer Ud Din, Christian Becker, Kerstin Becker, Holger Thiele, Ehtisham ul Haq Makhdoom, Pakeeza Arzoo Shaiq, Shahid M. Baig, Peter Nuernberg, Muhammad Sajid Hussain, Ghazala Kaukab Raja, Uzma Abdullah
Summary: Intellectual disability (ID) is a condition characterized by significant limitations in cognitive functioning and adaptive behavior, with genetic predisposition accounting for 50% of the etiology. In this study, two consanguineous Pakistani families presenting severe ID and developmental delay were recruited. Whole exome sequencing (WES) was performed on the probands and variants were prioritized based on population frequency, predicted pathogenicity, and functional relevance. Homozygous pathogenic variants in the genes MBOAT7 and TRAPPC9 were identified through WES data analysis. The pathogenicity of these variants was supported by co-segregation analysis and in silico tools. This study expands the mutation spectrum and provides additional evidence for the involvement of MBOAT7 and TRAPPC9 in the development of ID.
Article
Pediatrics
Michelle van Slobbe, Arie van Haeringen, Lisenka E. L. M. Vissers, Emilia K. Bijlsma, Julie W. Rutten, Manon Suerink, Esther A. R. Nibbeling, Claudia A. L. Ruivenkamp, Saskia Koene
Summary: This study evaluated the yield of whole-exome sequencing (WES) reanalysis in standard patient care in the Netherlands and found that it significantly increased the genetic diagnosis rate for patients. Most newly diagnosed patients had clinical consequences, and patients with dysmorphic features had a higher diagnostic yield in WES reanalysis.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Health Care Sciences & Services
A. L. Soilly, C. Robert-Viard, C. Besse, A. L. Bruel, B. Gerard, A. Boland, A. Piton, Y. Duffourd, J. Muller, C. Poe, T. Jouan, S. El Doueiri, L. Faivre, D. Bacq-Daian, B. Isidor, D. Genevieve, S. Odent, N. Philip, M. Doco-Fenzy, D. Lacombe, M. L. Asensio, J. F. Deleuze, C. Binquet, C. Thauvin-Robinet, C. Lejeune
Summary: The unit cost per exome sequencing (ES) diagnostic test for intellectual disability (ID) in the French setting was estimated to be 2,019.39 euros. Labor accounted for 50.7% of the total cost, while the analytical step represented 88% of the total cost. Sensitivity analyses showed that a decrease in the prices of the capture kit and sequencing support kit could lower the cost to 1,769 euros per ES diagnostic test for ID.
BMC HEALTH SERVICES RESEARCH
(2023)
Article
Medical Laboratory Technology
Wenqiu Zhang, Li Hu, Xinyi Huang, Dan Xie, Jiangfen Wu, Xiaoling Fu, Daiyi Liang, Shengwen Huang
Summary: This study identified five novel de novo mutations from four known ID-causing genes in four pediatric patients with unexplained intellectual disability (ID). These mutations were predicted to be deleterious and were located at highly conserved domains, potentially affecting the structure and function of these proteins.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Review
Genetics & Heredity
Maria Juliana Ballesta-Martinez, Virginia Perez-Fernandez, Vanesa Lopez-Gonzalez, Maria Jose Sanchez-Soler, Ana Teresa Serrano-Anton, Lidia Isolina Rodriguez-Pena, Maria Barreda-Sanchez, Lluis Armengol-Dulcet, Encarna Guillen-Navarro
Summary: Intellectual disability (ID) affects 1-3% of the population, with approximately 30-50% of cases having a genetic cause. Next-generation sequencing has provided high diagnostic potential for ID patients. This study evaluated the diagnostic yield and economic impact of clinical exome sequencing in 188 ID patients, highlighting a significant diagnostic yield (34%) and reduced costs and time to diagnosis. The findings support the early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Clinical Neurology
Leonie von Elsner, Guoliang Chai, Pauline E. Schneeberger, Frederike L. Harms, Christian Casar, Minyue Qi, Malik Alawi, Ghada M. H. Abdel-Salam, Maha S. Zaki, Florian Arndt, Xiaoxu Yang, Valentina Stanley, Maja Hempel, Joseph G. Gleeson, Kerstin Kutsche
Summary: The peripheral protein FRA10AC1 of the spliceosomal C complex plays a crucial role in neurodevelopment, with mutations potentially leading to intellectual disabilities and other symptoms.
Article
Clinical Neurology
Pauline E. Schneeberger, Sheela Nampoothiri, Tess Holling, Dhanya Yesodharan, Malik Alawi, A. S. Knisely, Thomas Mueller, Barbara Plecko, Andreas R. Janecke, Kerstin Kutsche
Summary: GARP and EARP are membrane-tethering heterotetramers located at the trans-Golgi network and recycling endosomes, mediating retrograde transport and endocytic recycling. Patients with VPS50 variants exhibit severe developmental delay, microcephaly, seizures, and liver abnormalities.
Article
Neurosciences
Mao-Qiang Tian, Xiao-Rong Liu, Si-Mei Lin, Jie Wang, Sheng Luo, Liang-Di Gao, Xiao-Bin Chen, Xiao-Yu Liang, Zhi-Gang Liu, Na He, Yong-Hong Yi, Wei-Ping Liao
Summary: Novel BRWD3 variants were identified in patients with idiopathic partial epilepsy (IPE), including two recurrent missense variants and one intronic variant close to splice site. These variants were found to be significantly associated with IPE and showed a higher frequency in patients compared to controls. Furthermore, missense variants located in specific domains of BRWD3 were associated with epilepsy, while destructive variants were associated with intellectual disability.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Olga Levchenko, Elena Dadali, Ludmila Bessonova, Nina Demina, Galina Rudenskaya, Galina Matyushchenko, Tatiana Markova, Inga Anisimova, Natalia Semenova, Olga Shchagina, Oxana Ryzhkova, Rena Zinchenko, Varvara Galkina, Victoria Voinova, Sabina Nagieva, Alexander Lavrov
Summary: Intellectual development disorder (IDD) is characterized by deficits in intellectual and adaptive functioning. This study investigated the genetic structure of IDD, particularly in patients with non-specific IDD. Hereditary forms of IDD accounted for a significant portion of non-specific IDD cases, with monogenic forms being the most common. Variants in genes associated with the BAF (SWI/SNF) complex were frequently identified. Whole-exome sequencing was found to be an efficient diagnostic method after standard examination of patients with IDD in Russia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Zahra Rashvand, Kimia Kahrizi, Hossein Najmabadi, Reza Najafipour, Mir Davood Omrani
Summary: Intellectual disability (ID) is a common feature of many rare disorders, which are highly heterogeneous and complex. The study identified a novel pathogenic splicing variant c.1441-1G>A in the C12orf4 gene in two Iranian patients with non-syndromic ID, contributing to a better understanding of the genotype-phenotype correlation in this very rare disease.
JOURNAL OF GENE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Iqra Ghulam Rasool, Muhammad Yasir Zahoor, Muhammad Iqbal, Aftab Ahmad Anjum, Fatima Ashraf, Hafiz Qamar Abbas, Hafiz Muhammad Azhar Baig, Tariq Mahmood, Wasim Shehzad
Summary: This study identified new variants in four different ID genes in consanguineous Pakistani families, with each variant showing a recessive pattern of inheritance. One of the variants found is associated with Knobloch syndrome, confirming the phenotype of this genetic disorder.
Article
Genetics & Heredity
Takuya Hiraide, Kaori Yamoto, Yohei Masunaga, Miki Asahina, Yusaku Endoh, Yumiko Ohkubo, Tomoko Matsubayashi, Satoshi Tsurui, Hidetaka Yamada, Kumiko Yanagi, Mitsuko Nakashima, Kouichi Hirano, Haruhiko Sugimura, Tokiko Fukuda, Tsutomu Ogata, Hirotomo Saitsu
Summary: Whole-exome sequencing (WES) was performed on 101 Japanese patients with unexplained developmental delay (DD) or intellectual disability (ID), leading to the identification of pathogenic variants, including copy number variants (CNVs) and somatic variants. The presence of autism spectrum disorder and external ear anomalies was associated with the detection of pathogenic variants, highlighting the importance of genetic testing in patients with these conditions.
Article
Genetics & Heredity
Irma Jarvela, Tuomo Maatta, Anushree Acharya, Juha Leppala, Shalini N. Jhangiani, Maria Arvio, Auli Siren, Minna Kankuri-Tammilehto, Hannaleena Kokkonen, Maarit Palomaki, Teppo Varilo, Mary Fang, Trevor D. Hadley, Angad Jolly, Tarja Linnankivi, Ritva Paetau, Anni Saarela, Reetta Kalviainen, Jan Olme, Liz M. Nouel-Saied, Diana M. Cornejo-Sanchez, Lorida Llaci, James R. Lupski, Jennifer E. Posey, Suzanne M. Leal, Isabelle Schrauwen
Summary: Research in the founder population of Finland revealed that de novo variants were the most common underlying cause of intellectual disability, with limited contribution of autosomal recessive intellectual disability to the etiology of ID, mainly influenced by founder and potential founder variations.
Article
Oncology
Joline Roze, Elena Sendino Garvi, Ellen Stelloo, Christina Stangl, Ferdinando Sereno, Karen Duran, Jolijn Groeneweg, Sterre Paijens, Hans Nijman, Hannah van Meurs, Luc van Lonkhuijzen, Jurgen Piek, Christianne Lok, Geertruida Jonges, Petronella Witteveen, Rene Verheijen, Gijs van Haaften, Ronald Zweemer, Glen Monroe
Summary: The study demonstrates a rapid method to establish patient-derived cell lines for drug screening in granulosa cell tumors. Combination treatment with alpelisib and chemotherapy showed promising results and should be further investigated as a potential effective treatment option in patients with granulosa cell tumors.
Review
Pharmacology & Pharmacy
Helen Roessler, Nine V. A. M. Knoers, Mieke M. van Haelst, Gijs van Haaften
Summary: There are around 7000 identified rare diseases, with less than 6% having an approved treatment option. Drug repurposing is a time-saving and cost-efficient method that can significantly reduce the risk of drug development for rare diseases. New strategies have been developed in recent years for a systematic and rational approach to drug repurposing.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Steven Hageman, Lisa Pennells, Francisco Ojeda, Stephen Kaptoge, Kari Kuulasmaa, Tamar de Vries, Zhe Xu, Frank Kee, Ryan Chung, Angela Wood, John William McEvoy, Giovanni Veronesi, Thomas Bolton, Paul Dendale, Brian A. Ference, Martin Halle, Adam Timmis, Panos Vardas, John Danesh, Ian Graham, Veikko Salomaa, Frank Visseren, Dirk De Bacquer, Stefan Blankenberg, Jannick Dorresteijn, Emanuele Di Angelantonio, Stephan Achenbach, Krasimira Aleksandrova, Pilar Amiano, Philippe Amouyel, Jonas Andersson, Stephan J. L. Bakker, Rui Bebiano Da Providencia Costa, Joline W. J. Beulens, Michael Blaha, Martin Bobak, Jolanda M. A. Boer, Catalina Bonet, Fabrice Bonnet, Marie-Christine Boutron-Ruault, Tonje Braaten, Hermann Brenner, Fabian Brunner, Eric J. Brunner, Mattias Brunstrom, Julie Buring, Adam S. Butterworth, Nadezda Capkova, Giancarlo Cesana, Christina Chrysohoou, Sandra Colorado-Yohar, Nancy R. Cook, Cyrus Cooper, Christina C. Dahm, Karina Davidson, Elaine Dennison, Augusto Di Castelnuovo, Chiara Donfrancesco, Marcus Doerr, Agnieszka Dorynska, Mats Eliasson, Gunnar Engstrom, Pietro Ferrari, Marco Ferrario, Ian Ford, Michael Fu, Ron T. Gansevoort, Simona Giampaoli, Richard F. Gillum, Agustin Gomez de la Camara, Guido Grassi, Per-Olof Hansson, Radu Huculeci, Kristian Hveem, Licia Iacoviello, M. Kamran Ikram, Torben Jorgensen, Bijoy Joseph, Pekka Jousilahti, J. Wouter Jukema, Rudolf Kaaks, Verena Katzke, Maryam Kavousi, Stefan Kiechl, Jens Klotsche, Wolfgang Koenig, Richard A. Kronmal, Ruzena Kubinova, Anna Kucharska-Newton, Kristi Lall, Nils Lehmann, David Leistner, Allan Linneberg, David Lora Pablos, Thiess Lorenz, Wentian Lu, Dalia Luksiene, Magnus Lyngbakken, Christina Magnussen, Sofia Malyutina, Alejandro Marin Ibanez, Giovanna Masala, Ellisiv B. Mathiesen, Kuni Matsushita, Tom W. Meade, Olle Melander, Haakon E. Meyer, Karel G. M. Moons, Conchi Moreno-Iribas, David Muller, Thomas Muenzel, Yury Nikitin, Borge G. Nordestgaard, Torbjorn Omland, Charlotte Onland, Kim Overvad, Chris Packard, Andrzej Pajak, Luigi Palmieri, Demosthenes Panagiotakos, Salvatore Panico, Aurora Perez-Cornago, Annette Peters, Arto Pietila, Hynek Pikhart, Bruce M. Psaty, Fosca Quarti-Trevano, J. Ramon Quiros Garcia, Elio Riboli, Paul M. Ridker, Beatriz Rodriguez, Miguel Rodriguez-Barranco, Annika Rosengren, Ronan Roussel, Carlotta Sacerdote, Susana Sans, Naveed Sattar, Catarina Schiborn, Boerge Schmidt, Ben Schoettker, Matthias Schulze, Joseph E. Schwartz, Randi Marie Selmer, Steven Shea, Martin J. Shipley, Sabina Sieri, Stefan Soderberg, Reecha Sofat, Abdonas Tamosiunas, Barbara Thorand, Taavi Tillmann, Anne Tjonneland, Tammy Y. N. Tong, Antonia Trichopoulou, Rosario Tumino, Hugh Tunstall-Pedoe, Anne Tybjaerg-Hansen, Joanna Tzoulaki, Amber van der Heijden, Yvonne T. van der Schouw, W. M. Monique Verschuren, Henry Voelzke, Christoph Waldeyer, Nicholas J. Wareham, Elisabete Weiderpass, Franz Weidinger, Philipp Wild, Johann Willeit, Peter Willeit, Tom Wilsgaard, Mark Woodward, Tanja Zeller, Dudan Zhang, Bin Zhou
Summary: The study aimed to develop, validate, and demonstrate an updated prediction model (SCORE2) to estimate 10-year cardiovascular disease risk in individuals without previous history of CVD or diabetes in Europe. The new algorithm, SCORE2, enhances the identification of individuals at higher risk of developing CVD across Europe by predicting first-onset CVD risk in European populations.
EUROPEAN HEART JOURNAL
(2021)
Article
Cardiac & Cardiovascular Systems
Tamar de Vries, Marie Therese Cooney, Randi M. Selmer, Steven H. J. Hageman, Lisa A. Pennells, Angela Wood, Stephen Kaptoge, Zhe Xu, Jan Westerink, Kjersti S. Rabanal, Grethe S. Tell, Haakon E. Meyer, Jannicke Igland, Inger Ariansen, Kunihiro Matsushita, Michael J. Blaha, Vijay Nambi, Ruth Peters, Nigel Beckett, Riitta Antikainen, Christopher J. Bulpitt, Majon Muller, Marielle H. Emmelot-Vonk, Stella Trompet, Wouter Jukema, Brian A. Ference, Martin Halle, Adam D. Timmis, Panos E. Vardas, Jannick A. N. Dorresteijn, Dirk De Bacquer, Emanuele Di Angelantonio, Frank L. J. Visseren, Ian M. Graham
Summary: The study developed and validated the SCORE2-OP risk model for estimating 5- and 10-year cardiovascular disease (CVD) risk in individuals aged over 70 years in four geographical regions. The models took into account various risk factors, were recalibrated to each region, and showed significant variation in CVD event risk across the four risk regions for different risk factor profiles.
EUROPEAN HEART JOURNAL
(2021)
Article
Psychiatry
Claudia Modenato, Kuldeep Kumar, Clara Moreau, Sandra Martin-Brevet, Guillaume Huguet, Catherine Schramm, Martineau Jean-Louis, Charles-Olivier Martin, Nadine Younis, Petra Tamer, Elise Douard, Fanny Thebault-Dagher, Valerie Cote, Audrey-Rose Charlebois, Florence Deguire, Anne M. Maillard, Borja Rodriguez-Herreros, Aurelie Pain, Sonia Richetin, Lester Melie-Garcia, Leila Kushan, Ana Silva, Marianne B. M. van den Bree, David E. J. Linden, Michael J. Owen, Jeremy Hall, Sarah Lippe, Mallar Chakravarty, Danilo Bzdok, Carrie E. Bearden, Bogdan Draganski, Sebastien Jacquemont
Summary: This study investigates the impact of multiple neurodevelopmental and psychiatric disorder-associated CNVs on brain anatomy, and identifies shared latent brain regions through principal component analysis. While CNVs exhibit unique brain patterns, they show some overlap in latent brain dimensions.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Surgery
Mellody Cooiman, Suzanne I. M. Alsters, Maeva Duquesnoy, Eric J. Hazebroek, Hanne J. Meijers-Heijboer, Harvinder Chahal, Johanne Le Beyec-Le Bihan, Karine Clement, Hedi Soula, Alex Blakemore, Christine Poitou, Mieke M. van Haelst
Summary: This multicenter study compares the weight loss and regain outcomes in bariatric surgery patients with MC4R variants to matched controls. The study reveals that cases with MC4R variants show inferior weight outcomes after SG compared to RYGB, highlighting the need for lifelong management to prevent relapse.
Article
Cardiac & Cardiovascular Systems
Tamar de Vries, Manon C. Stam-Slob, Ron J. G. Peters, Yolanda van der Graaf, Jan Westerink, Frank L. J. Visseren
Summary: This study aimed to evaluate whether individual baseline risk influences the relative treatment effects of medication in two large trials. The results showed that there was no significant interaction between baseline risk and relative treatment effect in certain aspects, while there was a significant interaction in others. It is recommended to systematically assess the impact of individual baseline risk in randomized clinical trials.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Genetics & Heredity
Eline A. Verberne, Jonne M. Westermann, Tamar de Vries, Ginette M. Ecury-Goossen, Shirley M. Lo-A-Njoe, Meindert E. Manshande, Sonja Faries, Hans D. Veenhuis, Patricia Philippi, Farah A. Falix, Irsa Rosina-Angelista, Maria Ponson-Wever, Louise Rafael-Croes, Patricia Thorsen, Eric Arends, Maartje de Vroomen, Sietse Q. Nagelkerke, Martijn Tilanus, Lars T. van der Veken, Karin Huijsdens-van Amsterdam, Anne-Marie Van der Kevie-Kersemaekers, Marielle Alders, Marcel M. A. M. Mannens, Mieke M. van Haelst
Summary: This study established a bi-annual joint pediatric-genetics clinic in the Dutch Caribbean, evaluating the diagnostic yield and clinical utility of genetic testing for patients with rare diseases in this resource-limited setting. The results showed a reasonably high molecular diagnostic yield and impact on clinical management for the majority of patients, despite financial constraints. The approach of having a visiting clinical geneticist may serve as an example for others developing genetic services in similar settings.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Endocrinology & Metabolism
Eline S. van der Valk, Lotte Kleinendorst, Patric J. D. Delhanty, Bibian van der Voorn, Jenny A. Visser, M. M. van Haelst, Laura C. G. de Graaff, Martin Huisman, Anne White, Shosuke Ito, Kazumasa Wakamatsu, Yolanda B. de Rijke, Erica L. T. van den Akker, Anand M. Iyer, Elisabeth F. C. van Rossum
Summary: Patients with a novel POMC gene variant presented with obesity, hyperphagia, and hypocortisolism, related to an ACTH defect at the prohormone convertase 2 cleavage site. The study demonstrated that adequate cleavage of ACTH to alpha-MSH and d-alpha-MSH is also crucial for feeding control in humans.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Ozair Abawi, Emma C. Koster, Mila S. Welling, Sanne C. M. Boeters, Elisabeth F. C. van Rossum, Mieke M. van Haelst, Bibian van der Voorn, Cornelis J. de Groot, Erica L. T. van den Akker
Summary: This study investigated the resting energy expenditure and body composition characteristics of children and adolescents with severe obesity with or without underlying medical causes. The results showed large inter-individual differences in resting energy expenditure among patients, highlighting the importance of personalized treatment strategies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Letter
Biochemistry & Molecular Biology
Lynne Rumping, Raoul C. M. Hennekam, Marielle Alders, Mieke M. van Haelst
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Jian Gao, Conor McClenaghan, Imke Christiaans, Marielle Alders, Kirsten van Duinen, Mieke M. van Haelst, Gijs van Haaften, Colin G. Nichols
Summary: Cantu Syndrome is a rare disorder characterized by hypertrichosis, osteochondrodysplasia, and cardiomegaly. A recent study suggests that idiopathic lymphedema may actually be an initial presentation of Cantu Syndrome. Molecular phenotyping is necessary to confirm the relevance of identified variants.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Liselot van der Laan, Kathleen Rooney, Sadegheh Haghshenas, Ananilia Silva, Haley Mcconkey, Raissa Relator, Michael A. Levy, Irene Valenzuela, Laura Trujillano, Amaia Lasa-Aranzasti, Berta Campos, Neus Castells, Eline A. Verberne, Saskia Maas, Marielle Alders, Marcel M. A. M. Mannens, Mieke M. van Haelst, Bekim Sadikovic, Peter Henneman
Summary: JARID2 haploinsufficiency is associated with a distinct neurodevelopmental syndrome characterized by intellectual disability, developmental delay, autistic features, behavior abnormalities, cognitive impairment, hypotonia, and dysmorphic features. The study identified JARID2 as the driver gene for aberrant DNA methylation observed in 6p22-p24 microdeletions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pediatrics
Ozair Abawi, Rama J. Wahab, Lotte Kleinendorst, Lizette A. Blankers, Ammelies E. Brandsma, Elisabeth F. C. van Rossum, Bibian van der Voorn, Mieke M. van Haelst, Romy Gaillard, Erica L. T. van den Akker
Summary: This study aimed to assess the body mass index trajectories of children with genetic obesity and determine the optimal early age of onset of obesity (AoO) cut-offs for genetic screening. The results showed that the optimal AoO cut-off for nonsyndromic genetic obesity was 3.9 years, while for syndromic genetic obesity it was 4.7 years.
JOURNAL OF PEDIATRICS
(2023)
Article
Medicine, Research & Experimental
Agnies M. van Eeghen, Hilgo Bruining, Nicole I. Wolf, Arthur A. Bergen, Riekelt H. Houtkooper, Mieke M. van Haelst, Clara D. van Karnebeek
Summary: Rare neurogenetic disorders are common and often present with complex multiorgan comorbidity, affecting 3% of the population. Advances in genetic, -omics, and computational analysis enable earlier diagnosis and the development of treatment options such as gene therapy and drug repurposing. Targeted therapy can prevent the devastating manifestations of these disorders. The article discusses successes in diagnosis, prevention, and treatment, as well as barriers to implementing rare disease-specific therapies. New methodologies, care networks, and collaborative frameworks are proposed to optimize personalized genomic medicine for improving the lives of vulnerable patients.
COLD SPRING HARBOR MOLECULAR CASE STUDIES
(2022)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)