Article
Biochemistry & Molecular Biology
Dolores Martinez-Rubio, Isabel Hinarejos, Herminia Argente-Escrig, Clara Marco-Marin, Maria Ana Lozano, Nerea Gorria-Redondo, Vincenzo Lupo, Itxaso Marti-Carrera, Concepcion Miranda, Maria Vazquez-Lopez, Asuncion Garcia-Perez, Ana Victoria Marco-Hernandez, Miguel Tomas-Vila, Sergio Aguilera-Albesa, Carmen Espinos
Summary: Cerebellar atrophy is a common issue in pediatric neurology, and its genetic complexity has led to the discovery of new genes associated with the condition. This study identified known and novel gene variants in patients with early-onset cerebellar involvement, expanding our understanding of the genetic causes of this condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Mariana Santos, Joana Damasio, Susana Carmona, Joao Luis Neto, Nadia Dehghani, Leonor Correia Guedes, Clara Barbot, Jose Barros, Jose Bras, Jorge Sequeiros, Rita Guerreiro
Summary: This study performed whole-exome sequencing on families with hereditary cerebellar ataxia (HCA) to identify causal genes and discovered novel pathogenic variants associated with different clinical syndromes. It also highlighted the importance of distinguishing between autosomal dominant and autosomal recessive forms, and proposed common molecular pathways underlying cerebellar neurodegeneration.
Article
Clinical Neurology
Eliane Chouery, Cybel Mehawej, Sandra Sabbagh, Jamal Bleik, Andre Megarbane
Summary: In this study, we report a 9-month-old girl with EIEE who carries a homozygous missense mutation in the NECAP1 gene for the first time. Our findings broaden the clinical spectrum of NECAP1-related diseases.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Mingping Lan, Yanjuan Wang, Sixiu Li, Lili Zhao, Ping Liu, Wenguang Hu
Summary: Infantile epileptic spasms syndrome (IESS) is a common epileptic encephalopathy of infancy characterized by epileptic spasms, hypsarrhythmia, and developmental delay. Genetic factors, including mutations in the SETD1A gene, play a significant role in the development of IESS. This study reports a case of IESS caused by a de novo mutation in exon 12 of the SETD1A gene and provides a summary of the existing literature on SETD1A gene-related epilepsy.
FRONTIERS IN NEUROLOGY
(2023)
Article
Neurosciences
Petya Bogdanova-Mihaylova, Josephine Hebert, Sharon Moran, Michael Murphy, Deirdre Ward, Richard A. Walsh, Sinead M. Murphy
Summary: Establishing a molecular diagnosis for patients with progressive ataxia can be challenging due to genetic and clinical heterogeneity. The 5-year experience of the National Ataxia Clinic in Ireland shows that advanced genetic testing significantly improves diagnostic yield and should be considered in individuals with negative repeat expansion testing. Careful clinical phenotyping is crucial for appropriate genetic testing in selected patients in a timely manner.
Article
Biochemistry & Molecular Biology
Romina Romaniello, Ludovica Pasca, Elena Panzeri, Fulvio D'Abrusco, Lorena Travaglini, Valentina Serpieri, Sabrina Signorini, Chiara Aiello, Enrico Bertini, Maria Teresa Bassi, Enza Maria Valente, Ginevra Zanni, Renato Borgatti, Filippo Arrigoni
Summary: Pathogenic variants in the ITPR1 gene are associated with autosomal dominant spinocerebellar ataxia. Superior vermian and hemispheric cerebellar atrophy on MRI can be a distinguishing feature of ITPR1-related disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pediatrics
Dan Sun, Yan Liu, Wei Cai, Jiehui Ma, Kun Ni, Ming Chen, Cheng Wang, Yongchu Liu, Yuanyuan Zhu, Zhisheng Liu, Feng Zhu
Summary: This study investigated Epileptic encephalopathies (EEs) using Whole Exome Sequencing (WES) and found that combining the detection of disease-causing SNVs/Indels and CNVs can increase the diagnostic rate. Genetic causes were successfully identified in 46.6% of infants, with the majority of disease-causing variants inherited in a de novo pattern.
FRONTIERS IN PEDIATRICS
(2021)
Article
Clinical Neurology
Cecile Mignon-Ravix, Florence Riccardi, Geraldine Daquin, Pierre Cacciagli, Sylvie Lamoureux-Toth, Laurent Villard, Nathalie Villeneuve, Florence Molinari
Summary: Developmental and epileptic encephalopathies (DEE) are a group of neurodevelopmental disorders characterized by epileptic seizures associated with developmental delay or regression. We identified a novel homozygous protein-truncating variant in the NAPB gene that encodes the beta SNAP protein. Our findings strengthen the association between biallelic variants in NAPB and DEE and suggest including this gene in the targeted epilepsy gene panels used for routine diagnosis of unexplained epilepsy.
Article
Neurosciences
Dilsad Turkdogan, Ayberk Turkyilmaz, Gunes Sager, Gulten Ozturk, Olcay Unver, Merve Say
Summary: This study aimed to investigate the genetic causes of early infantile epileptic encephalopathies (EIEE) in Turkish children, most of whom had consanguineous parents. The results showed a higher diagnostic yield for whole exome sequencing, along with expanded phenotypes and potential candidate genes and copy number variants. Detailed electro-clinical phenotyping played a crucial role in the identification and counseling of affected families.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Isis Biembengut, Patricia Shigunov, Natalia F. Frota, Marcos R. Lourenzoni, Tatiana A. C. B. de Souza
Summary: The study investigates the impact of the R87C mutation on the structure of the WAVE regulatory complex (WRC) and reveals the potential mechanism by which the mutation impairs the stability and regulation of the WRC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Min-Yu Lan, Chin-Song Lu, Shey-Lin Wu, Ying-Fa Chen, Yueh-Feng Sung, Min-Chien Tu, Yung-Yee Chang
Summary: This study characterized the clinical and genetic features of HSP patients with concurrent cerebellar ataxia and identified causative mutations in multiple genes. The study revealed the genetic complexity and functional overlap in HSP with cerebellar involvement.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Jia Chen, Junfang Xiao, Ge Chen, Qiang Xu, Xingwu Wu, Lifeng Tian, Zhihui Huang, Cailin Xin, Yan Zhao, Zhen Guo, Yang Zou, Qiongfang Wu
Summary: This study reports two siblings from a Chinese family with progressive cerebellar atrophy and ataxia. Whole exome sequencing identified two compound heterozygous mutations in the MSTO1 gene. In vitro experiments showed that these mutations lead to reduced protein abundance and decreased mtDNA content. The siblings also exhibited low birth weights, learning difficulties, and dysarthria in addition to ataxia and delayed motor development.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Giulia Coarelli, Thomas Wirth, Christine Tranchant, Michel Koenig, Alexandra Durr, Mathieu Anheim
Summary: This narrative review provides an update on the management of inherited cerebellar ataxias (ICAs), including main clinical entities, genetic analysis strategies, and recent therapeutic developments. It offers support for diagnosis, genetic counseling, and therapeutic management of ICAs in clinical practice.
JOURNAL OF NEUROLOGY
(2023)
Review
Genetics & Heredity
Mateusz Biela, Malgorzata Rydzanicz, Krystyna Szymanska, Karolina Pieniawska-Smiech, Aleksandra Lewandowicz-Uszynska, Joanna Chruszcz, Lucyna Benben, Malgorzata Kuzior-Plawiak, Pawel Szyld, Aleksandra Jakubiak, Leszek Szenborn, Rafal Ploski, Robert Smigiel
Summary: Variants in residue 756 of the ATP1A3 gene can cause recurrent neurological decompensations triggered by fever, characterized by severe hypotonia, ataxia, dysarthria, and orofacial symptoms. Recovery is slow and persistent symptoms include cerebellar ataxia, dysarthria, and dystonic and choreiform movements.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Clinical Neurology
Lucie Sedlackova, Katalin Sterbova, Marketa Vlckova, Pavel Seeman, Jana Zarubova, Petr Marusic, Pavel Krsek, Hana Krijtova, Alena Musilova, Petra Lassuthova
Summary: In this study, whole exome sequencing (WES) was performed to identify causal variants for developmental and epileptic encephalopathies (DEEs) in patients whose genetic diagnosis was not determined by gene panel testing. The results showed that WES can successfully identify disease-causing variants, even after inconclusive gene panel testing. Detailed clinical evaluations and phenotype-genotype correlation studies were conducted to better understand the rare subtypes of DEEs.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Endocrinology & Metabolism
Aubin Garcia, Marie Legendre, Sandra Chantot-Bastaraud, Jean-Pierre Siffroi, Sophie Christin-Maitre
Summary: This case report describes a 46,XY Difference of Sexual Development (DSD) individual with a female phenotype, primary amenorrhea, facial dysmorphia and mental retardation. Gene sequencing revealed two heterozygous loss-of-function mutations in the HSD17B3 enzyme. Additionally, microarray analysis identified a 37Mb segmental 3p duplication and a recurrent 16p13.11 microduplication. The HSD17B3 mutations were identified only in adulthood, and the patient's severe mental retardation and facial dysmorphia were due to genetic abnormalities different from the ones involved in her DSD.
ANNALES D ENDOCRINOLOGIE
(2023)
Article
Genetics & Heredity
Stefanie Brock, Annie Laquerriere, Florent Marguet, Scott J. Myers, Yuan Hongjie, Diana Baralle, Tim Vanderhasselt, Katrien Stouffs, Kathelijn Keymolen, Sukhan Kim, James Allen, Gil Shaulsky, Jamel Chelly, Pascale Marcorelle, Jacqueline Aziza, Laurent Villard, Elise Sacaze, Marie C. Y. de Wit, Martina Wilke, Grazia Maria Simonetta Mancini, Ute Hehr, Derek Lim, Sahar Mansour, Stephen F. Traynelis, Claire Beneteau, Marie Denis-Musquer, Anna C. Jansen, Andrew E. Fry, Nadia Bahi-Buisson
Summary: This study aimed to further define the phenotypic spectrum of NMDAR-related malformations of cortical development (MCDs). Clinical, radiological, and molecular features of new and previously reported patients were analyzed and neuropathological findings were presented. The study provides new insights into the clinical and imaging features of NMDAR-related MCDs and contributes to our understanding of the underlying pathogenic mechanisms.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Madeleine Harion, Leila Qebibo, Audrey Riquet, Christelle Rougeot, Alexandra Afenjar, Catherine Garel, Malek Louha, Emmanuelle Lacaze, Frederique Audic-Gerard, Magali Barth, Patrick Berquin, Dominique Bonneau, Frederic Bourdain, Tiffany Busa, Estelle Colin, Jean-Marie Cuisset, Vincent Des Portes, Nathalie Dorison, Christine Francannet, Benedicte Heron, Cecile Laroche, Marine Lebrun, Julia Metreau, Sylvie Odent, Laurent Pasquier, Yaumara Perdomo Trujillo, Laurine Perrin, Lucile Pinson, Francois Rivier, Sabine Sigaudy, Christel Thauvin-Robinet, Ulrike Walther Louvier, Olivier Labayle, Diana Rodriguez, Stephanie Valence, Lydie Burglen
Summary: In this study, the phenotype and genotype of patients with Joubert syndrome (JS) carrying pathogenic variants on the CC2D2A gene were described. The study found that despite developmental delays, the majority of patients had normal intellectual efficiency and a low rate of other organ defects. Additionally, a specific pathogenic variant was linked to a more severe phenotype.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Urology & Nephrology
Hugo Bakis, Aurelien Trimouille, Agathe Vermorel, Cyril Goizet, Yaniss Belaroussi, Sacha Schutz, Guilhem Sole, Christian Combe, Marie-Laure Martin-Negrier, Claire Rigothier
Summary: Adults with mitochondrial disorders (MIDs) can also develop mitochondrial disorder-associated nephropathies (MIDANs), which are characterized by tubulointerstitial nephropathy or glomerular disease. Hypertension, albumin level, and vision abnormalities are associated with MIDANs.
CLINICAL KIDNEY JOURNAL
(2023)
Review
Genetics & Heredity
Clemence Jacquin, Emilie Landais, Celine Poirsier, Alexandra Afenjar, Ahmad Akhavi, Nathalie Bednarek, Caroline Benech, Adeline Bonnard, Damien Bosquet, Lydie Burglen, Patrick Callier, Sandra Chantot-Bastaraud, Christine Coubes, Charles Coutton, Bruno Delobel, Margaux Descharmes, Jean-Michel Dupont, Vincent Gatinois, Nicolas Gruchy, Sarah Guterman, Abdelkader Heddar, Lucas Herissant, Delphine Heron, Bertrand Isidor, Pauline Jaeger, Guillaume Jouret, Boris Keren, Paul Kuentz, Cedric Le Caignec, Jonathan Levy, Nathalie Lopez, Zoe Manssens, Dominique Martin-Coignard, Isabelle Marey, Cyril Mignot, Chantal Missirian, Celine Pebrel-Richard, Lucile Pinson, Jacques Puechberty, Sylvia Redon, Damien Sanlaville, Marta Spodenkiewicz, Anne-Claude Tabet, Alain Verloes, Gaelle Vieville, Catherine Yardin, Francois Vialard, Martine Doco-Fenzy
Summary: Chromosome 1p36 deletion syndrome is a common terminal deletion syndrome characterized by craniofacial features, developmental delay, hypotonia, epilepsy, and cardiac abnormalities. This study aims to evaluate the incidence of 1p36DS in the French population and compare it with other genetic syndromes, as well as refine the phenotype and improve patient management through genotype-phenotype correlation.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Eissa A. Faqeih, Malak Ali Alghamdi, Marwa A. Almahroos, Essa Alharby, Makki Almuntashri, Amnah M. Alshangiti, Prouteau Clement, Daniel G. Calame, Leila Qebibo, Lydie Burglen, Martine Doco-Fenzy, Mario Mastrangelo, Annalaura Torella, Filippo Manti, Vincenzo Nigro, Ziegler Alban, Ghadeer Saleh Alharbi, Jamil Amjad Hashmi, Rawya Alraddadi, Razan Alamri, Tadahiro Mitani, Barth Magalie, Zeynep Coban-Akdemir, Bilgen Bilge Geckinli, Davut Pehlivan, Antonio Romito, Vasiliki Karageorgou, Javier Martini, Estelle Colin, Dominique Bonneau, Aida Bertoli-Avella, James R. Lupski, Annalisa Pastore, Roy W. A. Peake, Ashraf Dallol, Majid Alfadhel, Naif A. M. Almontashiri
Summary: Genetic causes were identified in 10 patients with syndromic neurodevelopmental disorders, resulting in the discovery of two novel rare disease genes, HECTD4 and UBE3C. These findings expand the association of the HECT E3 ligase group with neurodevelopmental syndromes and provide insights into the missing heritability in patients with Angelman syndrome-like clinical diagnoses.
GENETICS IN MEDICINE
(2023)
Article
Acoustics
R. Hagege, K. Krajden Haratz, G. Malinger, L. Ben-Sira, Z. Leibovitz, D. Heron, L. Burglen, R. Birnbaum, S. Valence, B. Keren, L. Blumkin, J. -m. Jouannic, T. Lerman-Sagie, C. Garel
Summary: This retrospective multicenter study aimed to investigate the prenatal diagnosis of mild forms of tubulinopathy and define the ultrasound and MRI features that can facilitate this diagnosis. The main ultrasound criteria included midline distortion, ventricular asymmetry, dysmorphic and/or dilated frontal horn(s), and abnormal sulcation. The main MRI criteria were midline distortion, distortion of the cavum septi pellucidi, ventricular asymmetry, dilatation and/or distortion, dysmorphic and/or dilated frontal horn(s), and abnormal sulcation. Mutations were found in TUBB3, TUBB, TUBB2B, or TUBA1A genes. Most findings could be visualized on ultrasound. The prenatal diagnosis of mild tubulinopathy is challenging but important for prenatal counseling.
ULTRASOUND IN OBSTETRICS & GYNECOLOGY
(2023)
Article
Biology
Lydie Burglen, Evelien Van Hoeymissen, Leila Qebibo, Magalie Barth, Newell Belnap, Felix Boschann, Christel Depienne, Katrien De Clercq, Andrew G. L. Douglas, Mark P. Fitzgerald, Nicola Foulds, Catherine Garel, Ingo Helbig, Katharina Held, Denise Horn, Annelies Janssen, Angela M. Kaindl, Vinodh Narayanan, Christina Prager, Mailys Rupin-Mas, Alexandra Afenjar, Siyuan Zhao, Vincent Th Ramaekers, Sarah M. Ruggiero, Simon Thomas, Stephanie Valence, Lionel Van Maldergem, Tibor Rohacs, Diana Rodriguez, David Dyment, Thomas Voets, Joris Vriens
Summary: TRPM3 is a plasma membrane cation channel that is sensitive to temperature and neurosteroids and is expressed in various types of cells. Rare variants in TRPM3 have been found in individuals with developmental and epileptic encephalopathy, but the connection between TRPM3 activity and neurological disorders is not well understood. In this study, we identified additional heterozygous missense variants in TRPM3 in 10 patients with a range of neurodevelopmental symptoms. These variants cause a gain-of-function phenotype, leading to increased channel activity and altered calcium levels in cells. Treatment with the TRPM3 antagonist primidone reduced the increased channel activity, suggesting that TRPM3 antagonists could be a potential therapy for these disorders.
Article
Genetics & Heredity
Burak Tepe, Erica L. Macke, Marcello Niceta, Monika Weisz Hubshman, Oguz Kanca, Laura Schultz-Rogers, Yuri A. Zarate, G. Bradley Schaefer, Jorge Luis Granadillo De Luque, Daniel J. Wegner, Benjamin Cogne, Brigitte Gilbert-Dussardier, Xavier Le Guillou, Eric J. Wagner, Lynn S. Pais, Jennifer E. Neil, Ganeshwaran H. Mochida, Christopher A. Walsh, Nurit Magal, Valerie Drasinover, Mordechai Shohat, Tanya Schwab, Chris Schmitz, Karl Clark, Anthony Fine, Brendan Lanpher, Ralitza Gavrilova, Pierre Blanc, Lydie Burglen, Alexandra Afenjar, Dora Steel, Manju A. Kurian, Prab Prabhakar, Sophie Gosswein, Nataliya Di Donato, Enrico S. Bertini, Michael F. Wangler, Shinya Yamamoto, Marco Tartaglia, Eric W. Klee, Hugo J. Bellen
Summary: This study discovered that the Integrator complex is involved in the processing of various types of RNAs and that INTS11 is the catalytic subunit responsible for RNA cleavage. Mutations in INTS11 have been found to be associated with developmental delay, intellectual disability, impaired motor development, and brain atrophy. The study used Drosophila as a model organism to investigate the effects of different variants of INTS11.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Clinical Neurology
M. Gafner, C. Garel, Z. Leibovitz, S. Valence, K. Krajden Haratz, R. Oegema, G. M. S. Mancini, D. Heron, E. Bueltmann, L. Burglen, D. Rodriguez, T. A. G. M. Huisman, M. H. Lequin, A. Arad, D. Kidron, M. Muqary, L. Gindes, D. Lev, E. Boltshauser, T. Lerman-Sagie
Summary: This study investigates medullary tegmental cap dysplasia, a rare brainstem malformation, through a multicenter retrospective study of 13 patients. Different shapes of the cap and multiple etiologies and pathophysiology were found. The study provides clinical and pathological characteristics of this unique malformation.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Article
Genetics & Heredity
Florence Riant, Lydie Burglen, Michaelle Corpechot, Julien Robert, Alexandra Durr, Guilhem Sole, Florence Petit, Cecile Freihuber, Olivier De Marco, Catherine Sarret, Giovanni Castelnovo, Francoise Devillard, Alexandra Afenjar, Benedicte Heron, Elisabeth Tournier Lasserve
Summary: Loss of function variants in the CACNA1A gene can cause a range of neurological disorders. This study investigated the potential effects of 11 unknown variants on splicing. In silico predictions and Sanger sequencing confirmed the presence of abnormal transcripts in 10 out of 11 patients, with nine being classified as deleterious. Targeted next-generation RNA sequencing successfully obtained the full cDNA sequence of CACNA1A and detected most of the abnormally spliced transcripts.
Article
Clinical Neurology
Cecile Mignon-Ravix, Florence Riccardi, Geraldine Daquin, Pierre Cacciagli, Sylvie Lamoureux-Toth, Laurent Villard, Nathalie Villeneuve, Florence Molinari
Summary: Developmental and epileptic encephalopathies (DEE) are a group of neurodevelopmental disorders characterized by epileptic seizures associated with developmental delay or regression. We identified a novel homozygous protein-truncating variant in the NAPB gene that encodes the beta SNAP protein. Our findings strengthen the association between biallelic variants in NAPB and DEE and suggest including this gene in the targeted epilepsy gene panels used for routine diagnosis of unexplained epilepsy.
Article
Genetics & Heredity
Mario Abaji, Cecile Mignon-Ravix, Svetlana Gorokhova, Pierre Cacciagli, Jeremie Mortreux, Florence Molinari, Brigitte Chabrol, Sabine Sigaudy, Laurent Villard, Florence Riccardi
Summary: The TRAPP complexes are involved in intracellular transport and are related to ultra-rare human diseases called TRAPPopathies. Pathogenic variants in 8 genes encoding TRAPP proteins have been associated with neurodevelopmental disorders. This report describes a new protein-truncating variant in the TRAPPC2L gene found in two affected siblings, providing important genetic evidence and insights into the TRAPPC2L phenotype. The TRAPPC2L syndrome is characterized by severe neurodevelopmental disorder and variable muscle involvement, suggesting it belongs to the clinical entity of rare congenital muscular dystrophies.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Multidisciplinary Sciences
Deepak Khatri, Audrey Putoux, Audric Cologne, Sophie Kaltenbach, Alicia Besson, Eloise Bertiaux, Justine Guguin, Adele Fendler, Marie A. Dupont, Clara Benoit-Pilven, Leila Qebibo, Samira Ahmed-Elie, Severine Audebert-Bellanger, Pierre Blanc, Thomas Rambaud, Martin Castelle, Gaelle Cornen, Sarah Grotto, Agnes Guet, Laurent Guibaud, Caroline Michot, Sylvie Odent, Lyse Ruaud, Elise Sacaze, Virginie Hamel, Remy Bordonne, Anne -Louise Leutenegger, Patrick Edery, Lydie Burglen, Tania Attie-Bitach, Sylvie Mazoyer, Marion Delous
Summary: In the human genome, 750 genes contain one intron excised by the minor spliceosome. Mutations in the noncoding gene RNU4ATAC have been found in several syndromes. This study reveals bi-allelic RNU4ATAC mutations in patients with Joubert syndrome, expanding the spectrum of RNU4ATAC-associated disorders and suggesting ciliary dysfunction as a downstream mechanism of minor splicing defects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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)