Article
Clinical Neurology
Seda Susgun, Emrah Yucesan, Beyza Goncu, Sevde Hasanoglu Sayin, Umit Yasar Kina, Cemil Ozgul, Omer Faruk Duzenli, Ozcan Kocaturk, Mustafa Calik, Ugur Ozbek, Sibel Aylin Ugur Iseri
Summary: In this study, a genetic analysis of a large consanguineous family with neurodevelopmental disorders (NDDs) identified gene variants associated with NDD and Unverricht-Lundborg disease (ULD). The findings highlight the use of exome sequencing as the first-line diagnostic test for NDD individuals, but also emphasize the importance of customized approaches for specific diseases like ULD to aid in diagnosis and genetic counseling.
NEUROLOGICAL SCIENCES
(2023)
Review
Genetics & Heredity
Anushree Acharya, Isabelle Schrauwen, Suzanne M. Leal
Summary: Hearing impairment is a common sensory disability with high genetic heterogeneity. Non-syndromic hearing impairment is mainly caused by autosomal recessive inheritance. Populations with high rates of consanguinity have been crucial in identifying hearing impairment-related genes.
Article
Biochemistry & Molecular Biology
Hussein Algahtani, Bader Shirah, Ikram Ullah, Mohammad H. Al-Qahtani, Angham Abdulrahman Abdulkareem, Muhammad Imran Naseer
Summary: This study reported the clinical features and genetic diagnosis of autosomal recessive cerebellar ataxia with spasticity caused by a rare mutation in the GBA2 gene in a large consanguineous Saudi family. The homozygous variant c.2618G>A was identified in affected members of the family through whole exome sequencing and Sanger sequencing. The identified mutation causes loss of function and is classified as pathogenic, contributing further evidence to support its pathogenicity.
Article
Biochemical Research Methods
Emmanuel Sapin, Matthew C. Keller
Summary: A generic algorithm is proposed for addressing pairwise comparison problems in genomics, which breaks a large problem into smaller ones for massive parallelization. The efficiency of this approach was demonstrated in calling identical by descent segments in the UK Biobank dataset, with significant time and memory savings compared to the standard approach.
Article
Ophthalmology
Zohra Chibani, Imen Zone Abid, Peter Soderkvist, Jamel Feki, Mounira Hmani Aifa
Summary: This study identified a novel SLC4A11 gene mutation associated with CHED and confirmed its pathogenicity. The mutation may lead to disruptions in osmolarity balance and structural rearrangements in the protein, providing more insights into genotype-phenotype correlations.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Genetics & Heredity
Hammad Yousaf, Ambrin Fatima, Zafar Ali, Shahid M. Baig, Mathias Toft, Zafar Iqbal
Summary: This study reports a novel pathogenic variant in the GRM1 gene in a consanguineous Pakistani family with partially overlapping clinical features of SCAR13. In addition, the family presented quadrupedal gait and non-progressive symptoms, which have not been recognized previously.
Article
Medical Laboratory Technology
Mahdiyeh Moudi, Mohammad Yahya Vahidi Mehrjardi, Hossein Hozhabri, Zahra Metanat, Seyed Mehdi Kalantar, Mohsen Taheri, Nasrin Ghasemi, Mohammadreza Dehghani
Summary: A study reveals genetic mutations in patients with intellectual disability in Iranian consanguineous families. Filtering the data from whole-exome sequencing identified pathogenic mutations in the CEP290, FBXO31, and TIMM50 genes in the patients.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Endocrinology & Metabolism
Tobias Stauber, Lena Wartosch, Svenja Vishnolia, Ansgar Schulz, Uwe Kornak
Summary: After discovering a high level of v-ATPase complexes in the osteoclast ruffled membrane, it was found that the chloride/proton-exchanger ClC-7 could be responsible for transporting the negative charge. CLCN7 pathogenic variants were found in individuals with autosomal recessive osteopetrosis (ARO) and heterozygous pathogenic variants were identified as the exclusive cause of autosomal dominant osteopetrosis type 2 (ADO2). The electrophysiological properties of ClC-7 were also elucidated, showing that missense variants could lead to reduced chloride currents.
Review
Genetics & Heredity
Gabriela Roldao Correia-Costa, Ana Mondadori dos Santos, Nicole de Leeuw, Sumara Zuanazi Pinto Rigatto, Vera Maria Santoro Belangero, Carlos Eduardo Steiner, Vera Lucia Gil-da-Silva-Lopes, Tarsis Paiva Vieira
Summary: In this study, a child with primary microcephaly and nephropathic cystinosis was identified to have pathogenic variants in two genes through whole exome sequencing. This highlights the importance of searching for multilocus pathogenic variations in patients with complex phenotypes.
Article
Multidisciplinary Sciences
Cherine Charfeddine, Nadia Laroussi, Rahma Mkaouar, Raja Jouini, Olfa Khayat, Aladin Redissi, Amor Mosbah, Hamza Dallali, Achraf Chedly Debbiche, Anissa Zaouak, Sami Fenniche, Sonia Abdelhak, Houda Hammami-Ghorbel
Summary: A study investigated a consanguineous Tunisian family with two sisters presenting with Erythrokeratodermia variabilis (EKV) and identified a novel pathogenic mutation in the NIPAL4 gene. This mutation was predicted to destabilize the NIPA4 protein and perturb Mg2+ transport, implicating the potential role of NIPAL4 in the development and maintenance of the epidermal barrier function. These results expand the clinical phenotype associated with NIPAL4 mutation and support the hypothesis of NIPAL4 as the main candidate gene for EKV-like Autosomal Recessive Congenital Ichthyosis (ARCI) phenotype.
Article
Genetics & Heredity
Wei Xu, Ming Xu, Qinqin Yin, Chuangyi Liu, Qiuxiang Cao, Yun Deng, Sulai Liu, Guiyun He
Summary: A novel missense variant in the TUB gene was identified as the pathogenic basis for autosomal recessive retinitis pigmentosa in a Chinese consanguineous family. This is the first report of its kind for RP.
BMC MEDICAL GENOMICS
(2023)
Article
Biochemistry & Molecular Biology
Muhammad Asif, Chien-Chun Chiou, Malik Fiaz Hussain, Manzoor Hussain, Zureesha Sajid, Muhammad Gulsher, Afifa Raheem, Adil Khan, Nasreen Nasreen, Andrzej Kloczkowski, Mubashir Hassan, Furhan Iqbal, Chien-Chin Chen
Summary: This study reported the genetic basis of CMT in consanguineous Pakistani families, identifying mutations in GAPD1 and MFN2 genes as the cause of the disease.
DNA AND CELL BIOLOGY
(2023)
Article
Obstetrics & Gynecology
Pingping Chen, Hexige Saiyin, Ruona Shi, Bin Liu, Xu Han, Yuping Gao, Xiantao Ye, Xiaofei Zhang, Yu Sun
Summary: The study identified a critical role of the SPACAI gene in globozoospermia, expanding the spectrum of causative genes. Additionally, evidence was provided for ICSI clinical outcomes in patients with SPACAI deficiency, potentially guiding treatment strategies. The study also explored the pathogenesis of globozoospermia caused by SPACAI deficiency.
HUMAN REPRODUCTION
(2021)
Article
Psychiatry
Alyson Zwicker, Janice M. Fullerton, Niamh Mullins, Frances Rice, Danella M. Hafeman, Neeltje E. M. van Haren, Nikita Setiaman, John A. Merranko, Benjamin I. Goldstein, Alessandra G. Ferrera, Emma K. Stapp, Elena de la Serna, Dolores Moreno, Gisela Sugranyes, Sergio Mas Herrero, Gloria Roberts, Claudio Toma, Peter R. Schofield, Howard J. Edenberg, Holly C. Wilcox, Melvin G. McInnis, Victoria Powell, Lukas Propper, Eileen Denovan-Wright, Guy Rouleau, Josefina Castro-Fornieles, Manon H. J. Hillegers, Boris Birmaher, Anita Thapar, Philip B. Mitchell, Cathryn M. Lewis, Martin Alda, John I. Nurnberger, Rudolf Uher
Summary: The authors found that polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders. PGSs for neuroticism and subjective well-being are significantly associated with the onsets of disorders, and PGSs for psychiatric illness have limited predictive power when family history is known.
AMERICAN JOURNAL OF PSYCHIATRY
(2023)
Article
Environmental Sciences
Mathieu Renaud, Hamza El Morabet, Filipa Reis, Pedro Martins da Silva, Steven Douglas Siciliano, Jose Paulo Sousa, Tiago Natal-da-Luz
Summary: Soils are important habitats for a variety of plants and animals, but human activities can lead to high concentrations of metals in soil, posing a threat to ecosystems and the services they provide. Current regulatory guidelines focus on single species responses to individual metals, while neglecting indirect effects due to the inter-connected nature of ecosystems.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Biochemistry & Molecular Biology
Karuna R. M. van der Meij, Annabel Njio, Linda Martin, Janneke T. Gitsels-van der Wal, Mireille N. Bekker, Elsbeth H. van Vliet-Lachotzki, A. Jeanine E. M. van der Ven, Adriana Kater-Kuipers, Danielle R. M. Timmermans, Erik A. Sistermans, Robert-Jan H. Galjaard, Lidewij Henneman
Summary: Dutch pregnant women show high rates of informed decision-making and perceived freedom to choose regarding fetal aneuploidy screening, suggesting little concern about routinization of NIPT. Differences were found in personal and societal perspectives on Down syndrome between test-acceptors and test-decliners.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Elisa Garcia, Lidewij Henneman, Janneke T. Gitsels-van der Wal, Linda Martin, Isabel Koopmanschap, Mireille N. Bekker, Danielle R. M. Timmermans
Summary: The study found that while NIPT can improve accuracy in screening, uncertainty about fetal health, lack of treatment for detected disorders, and the ability to obtain information through fetal anomaly scans support the view that NIPT is not an obligation of responsible motherhood. Woman's acceptance of NIPT is considered a free decision based on the information needed to be a good mother for her child and family, and may change as NIPT expands to cover treatable or preventable conditions.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Eline A. Verberne, Lieke M. van den Heuvel, Maria Ponson-Wever, Maartje de Vroomen, Meindert E. Manshande, Sonja Faries, Ginette M. Ecury-Goossen, Lidewij Henneman, Mieke M. van Haelst
Summary: Research focused on the perspectives of patients and parents regarding genetic testing and its implications has been biased towards Europe, Canada, the United States, Australia, and New Zealand. In order to address this knowledge gap, this study explored the experiences and needs of parents in the Dutch Caribbean who received a genetic diagnosis for their child with a rare disease. The findings suggest that, despite limited availability of healthcare and support services, receiving a genetic diagnosis was valuable for most parents. Additionally, the study identified specific aspects related to the Dutch Caribbean setting, such as coping through faith and religion, social stigma, and being the only one on the island with a specific genetic disorder.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Engineering, Biomedical
Beatriz Molina-Martinez, Laura-Victoria Jentsch, Fulya Ersoy, Matthijs van der Moolen, Stella Donato, Torbjorn Ness, Peter Heutink, Peter D. Jones, Paolo Cesare
Summary: Three-dimensional cell technologies are emerging tools for studying the complexity of the nervous system. This study presents a novel approach using glass microfluidic microelectrode arrays to non-invasively record electrical activity in engineered 3D neuronal cultures. The platform enables high-throughput studies on the functional, morphological, and molecular details of neurological diseases and their potential treatment by therapeutic compounds.
Article
Biochemistry & Molecular Biology
Diewertje Houtman, Boy Vijlbrief, Marike Polak, Jacqueline Pot, Petra Verhoef, Martina Cornel, Sam Riedijk
Summary: This study examines the outcomes of a public dialogue project about Human Germline Genome Editing (HGGE) in the Netherlands. The results show that the majority of the Dutch population agrees with the use of HGGE to prevent severe genetic diseases, but not for protection against infectious diseases or enhancement. Participation in dialogue appears to reduce negative opinions about HGGE, but there is no evidence that it changes acceptance rates.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Richelle A. C. M. Olde Keizer, Abderrahim Marouane, A. Chantal Deden, Wendy A. G. Van Zelst-Stams, Willem P. de Boode, Willem R. Keusters, Lidewij Henneman, Johannes Kristian Ploos van Amstel, Gerardus W. J. Frederix, Lisenka E. L. M. Vissers
Summary: This study aims to assess the impact of implementing Whole Exome Sequencing (WES) on healthcare costs for patients in the Neonatal Intensive Care Unit. The results show that patients who received genetic testing had higher healthcare costs compared to those without genetic testing. Modeling scenarios suggest that performing trio-WES for patients with congenital anomalies will lead to a limited increase in overall healthcare budget.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Article
Multidisciplinary Sciences
Ivy van Dijke, Carla G. van El, Phillis Lakeman, Mariette Goddijn, Tessel Rigter, Martina C. Cornel, Lidewij Henneman
Summary: Implementation of reproductive and genetic technologies in Dutch healthcare is slow, influenced by restrictive legislation, broad support for people living with disabilities, values of an egalitarian society, and limited commercialization. Stakeholders have varying views on new technologies and the ways they should be implemented, involving an organized collective learning process.
Correction
Biochemistry & Molecular Biology
Diewertje Houtman, Boy Vijlbrief, Marike Polak, Jacqueline Pot, Petra Verhoef, Martina Cornel, Sam Riedijk
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Julie Lake, Caroline Warly Solsberg, Jonggeol Jeffrey Kim, Juliana Acosta-Uribe, Mary B. Makarious, Zizheng Li, Kristin Levine, Peter Heutink, Chelsea X. Alvarado, Dan Vitale, Sarang Kang, Jungsoo Gim, Kun Ho Lee, Stefanie D. Pina-Escudero, Luigi Ferrucci, Andrew B. Singleton, Cornelis Blauwendraat, Mike A. Nalls, Jennifer S. Yokoyama, Hampton L. Leonard
Summary: This study conducted the largest multi-ancestry genome-wide association study (GWAS) to date, including European, East Asian, African American, and Caribbean Hispanic populations. The findings identified two novel disease-associated loci and fine-mapped nine loci with high posterior probability. The study also compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population.
MOLECULAR PSYCHIATRY
(2023)
Article
Genetics & Heredity
Marleen E. Jansen, Tessel Rigter, Thom M. C. Fleur, Patrick C. Souverein, W. M. Monique Verschuren, Susanne J. Vijverberg, Jesse J. Swen, Wendy Rodenburg, Martina C. Cornel
Summary: Pharmacogenomic testing is used to prevent adverse drug reactions, particularly in statin treatment. This study aimed to investigate the usefulness of pre-emptive pharmacogenomic screening in primary care, focusing on the SLCO1B1 c.521T>C genotype as a risk factor for adverse drug reactions. However, the study did not find an association between the SLCO1B1 c.521T>C genotype and changes in statin therapy in primary care. Prospective data collection is needed to better evaluate the predictive value of the SLCO1B1 c.521T>C genotype on adverse drug reactions.
Article
Biochemistry & Molecular Biology
Janneke M. L. Kuiper, Pascal Borry, Danya F. Vears, Hilde Van Esch, Martina C. Cornel, Ine Van Hoyweghen
Summary: The implementation of next-generation sequencing (NGS) in diagnostic practice has led to ongoing debates on how to construct and perform good genomic care. Our qualitative fieldwork at two large European centres for human genetics revealed conflicting beliefs, norms, and actions regarding NGS practices. Ambivalence was found around clinical boundaries, the value of NGS results, and the application of guidelines. Acknowledging and addressing these ambivalent perspectives can lead to more informed and transparent genetic care practices.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Hemmo A. F. Yska, Lidewij Henneman, Rinse W. Barendsen, Marc Engelen, Stephan Kemp
Summary: This study investigates the attitudes of individuals with ALD towards sex-specific newborn screening for ALD. The majority favored screening both newborn boys and girls for ALD.
INTERNATIONAL JOURNAL OF NEONATAL SCREENING
(2023)
Article
Humanities, Multidisciplinary
Wendy Geuverink, Carla van El, Martina Cornel, Bert Jan Lietaert Peerbolte, Janneke Gitsels, Linda Martin
Summary: Human genome editing technologies are rapidly developing with potential implications that raise ethical and societal questions beyond the purview of scientists. Understanding the views of carriers of autosomal dominant disorders on human genome editing is crucial for regulatory and policy decisions. Through interviews and thematic analysis, we found that most participants were positive towards the safe use of somatic and heritable genome editing (SGE and HGE) to prevent severe genetic disorders, while acknowledging concerns about the societal and natural impacts of HGE. The exploration of views on HGE involved complex and ambivalent perspectives, requiring space for stakeholders to reflect and weigh values.
HUMANITIES & SOCIAL SCIENCES COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Diewertje Houtman, Wendy Geuverink, Isabel Rosalie Arianne Retel Helmrich, Boy Vijlbrief, Martina Cornel, Sam Riedijk
Summary: Given the potential large ethical and societal implications of human germline gene editing (HGGE), the urgent need for public and stakeholder engagement (PSE) has been emphasized. This short communication provides guidance for broad and inclusive PSE by emphasizing the importance of futures literacy. By asking hypothetical questions and exploring different futures, limitations in discussing whether or how HGGE should be implemented can be avoided. Futures literacy also helps in achieving societal alignment by considering diverse values and needs of the public.
JOURNAL OF COMMUNITY GENETICS
(2023)
Article
Pediatrics
Maurike Dorothea De Groot-van der Mooren, Brigitta Catharina Scheerman, Lukas Augustinus Johannes Rammeloo, Hester van Wieringen, Anne-Marie Van Wermeskerken, Roos van der Plas, Peter de Winter, Michel Emile Weijerman, Martina Cornelia Cornel, Anton Hubertus van Kaam
Summary: The uptake of prenatal aneuploidy screening for DS is increasing worldwide, but neonatal mortality and morbidity in DS appears to be stable.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)