Article
Biochemistry & Molecular Biology
Hye In Ka, Mina Cho, Seung-Hae Kwon, Se Hwan Mun, Sora Han, Min Jung Kim, Young Yang
Summary: This study demonstrates the importance of ik in ciliogenesis in vivo for the first time. Loss of ik in zebrafish embryos displays various ciliopathy phenotypes with abnormal ciliary morphology in ciliary tissues. Ik affects ciliogenesis particularly in the proximal tubule.
CELL AND BIOSCIENCE
(2023)
Article
Genetics & Heredity
Chiara Frascarelli, Nadia Zanetti, Alessia Nasca, Rossella Izzo, Costanza Lamperti, Eleonora Lamantea, Andrea Legati, Daniele Ghezzi
Summary: Primary mitochondrial diseases are progressive genetic disorders characterized by mitochondrial dysfunction. They can be caused by mutations in nuclear genes or genetic defects in mitochondrial genome. Traditional sequencing methods are limited in detecting structural alterations in mtDNA, but new long-read NGS technologies show promise in this regard. This study presents optimized protocols using long-read Oxford Nanopore Technology for the detection of mtDNA structural alterations, which may become the method of choice for genetic studies on mtDNA.
FRONTIERS IN GENETICS
(2023)
Article
Biochemical Research Methods
Ron Zeira, Ron Shamir
Summary: This study introduces a model for the evolution of genomes with multiple gene copies, considering various types of operations including double-cut-and-joins, duplications, and deletions. It covers a broad spectrum of structural and numerical changes seen in tumor samples, and presents a method to reconstruct the full sequence of events during cancer evolution. The research advances the field by providing a more realistic approach to genome rearrangement analysis.
Article
Oncology
Ryuji Kojima, Esraa Hassan, Fumiko Ozawa, Chisato Yamada-Namikawa, Shino Ogawa, Shoko Mase, Shinobu Goto, Ryutaro Nishikawa, Hiroshi Inagaki, Yoichi Kato, Mayumi Sugiura-Ogasawara
Summary: The aim of the study was to investigate primary cilia in endometrial tissue during the menstrual cycle and their morphological changes in different grades of endometrial cancer. The study found that there were fewer ciliated cells and shorter primary cilia in highly malignant endometrial cancer tissues. The expression of OFD1 was significantly higher in high-grade endometrial cancer.
Review
Biochemistry & Molecular Biology
Manuela Morleo, Nunziana Pezzella, Brunella Franco
Summary: The balance of protein synthesis and degradation is crucial for cellular homeostasis and biological processes. Recent studies have revealed that centrosomal/ciliary proteins play a role in proteome control in response to spatial or microenvironmental stimuli. Understanding this balance in ciliopathies may lead to the identification of novel therapeutic targets for these genetic disorders.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Genetics & Heredity
Alanna Strong, Laurie Simone, Anthony Krentz, Courtney Vaccaro, Deborah Watson, Hayley Ron, Jennifer M. Kalish, Helio F. Pedro, Elaine H. Zackai, Hakon Hakonarson
Summary: Oral-facial-digital syndromes (OFDS) are a rare group of Mendelian disorders characterized by developmental abnormalities of the oral cavity, face, and digits caused by dysfunction of the primary cilium. These syndromes can be inherited in X-linked dominant, X-linked recessive, and autosomal recessive manners. Despite many causal genes being identified, up to 40% of OFDS cases have unknown genetic basis.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Biochemistry & Molecular Biology
Thomas F. Eleveld, Chaimaa Bakali, Paul P. Eijk, Phylicia Stathi, Lianne E. Vriend, Pino J. Poddighe, Bauke Ylstra
Summary: Large-scale chromosomal deletions are common in cancer and confer an oncogenic advantage, but the oncogenic drivers behind these deletions are difficult to identify. This study introduced a novel CRISPR-Cas9 technique to engineer large-scale deletions and create isogenic cell line models, successfully inducing deletions in neuroblastoma cell lines. The technique may provide valuable insights into the role of large-scale deletions in tumor development and growth.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Genetics & Heredity
Mamiko Yamada, Hisato Suzuki, Hiroshi Futagawa, Toshiki Takenouchi, Fuyuki Miya, Hiroshi Yoshihashi, Kenjiro Kosaki
Summary: This case report describes a 13-year-old patient with atrioventricular septal defect, moderate intellectual disability, epilepsy, and features of Oral-facial digital (OFD) syndrome. The patient has a de novo heterozygous variant in PRKACB gene. This report suggests that there is a significant phenotypic overlap between Cardioacrofacial dysplasia-2 (CADF2) and OFD syndrome, and an autosomal dominant pattern of inheritance should be considered during genetic counseling for these conditions.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Omer Yakar, Abdulgani Tatar
Summary: Oral-facial-digital syndrome XVII (OFDS XVII) is a rare genetic disorder characterized by developmental delay, facial and oral cavity abnormalities, polydactyly, cardiac anomaly, and other findings. It is caused by biallelic variants in the INTU gene and inherited in an autosomal recessive manner.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Clinical Neurology
Ricardo H. Roda, David Bargiela, Weiran Chen, Ken Perry, Ronald J. Ellis, David B. Clifford, Ajay Bharti, Asha R. Kallianpur, Michelli F. Oliveira, Monica M. Diaz, Leah H. Rubin, Christina Gavegnano, Justin C. McArthur, Ahmet Hoke, Michael Polydefkis
Summary: The study aimed to evaluate the correlation of large mtDNA deletions in skin samples of people with HIV with measures of neuropathy and prior exposure to therapy. Results showed a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) and sural nerve amplitude in PWH with HIV-associated sensory neuropathy.
Article
Genetics & Heredity
Chen Li, Xingwang Wang, Fake Li, Hongke Ding, Ling Liu, Ying Xiong, Chaoxiang Yang, Yan Zhang, Jing Wu, Aihua Yin
Summary: A novel nonsense variant in the OFD1 gene was identified in a suspected JBS family, broadening the genetic variation spectrum of JBS10 caused by OFD1. RNA-seq and protein structure prediction revealed that this variant may lead to a change in the structure of the OFD1 protein.
FRONTIERS IN GENETICS
(2023)
Article
Surgery
Masayuki Osawa, Yuhei Yamamoto, Munezumi Fujita, Taku Maeda, Emi Funayama
Summary: Oral-facial-digital syndrome type II is a rare autosomal recessive genetic disease characterized by features such as median cleft lip. The article describes a novel surgical method for repairing incomplete median cleft lip, which provided the patient with a good cosmetic outcome.
JOURNAL OF CRANIOFACIAL SURGERY
(2021)
Review
Pediatrics
Sara Alghamdi
Summary: This article provides a comprehensive review on the orofacial manifestations of Sanjad-Sakati syndrome (SSS) and emphasizes the importance of dental management in SSS individuals. The study found that the majority of the reported cases are from the Middle Eastern region.
Article
Radiology, Nuclear Medicine & Medical Imaging
Maia Proisy, Julie Powell, Catherine McCuaig, Ramy El Jalbout, Chantale Lapierre, Josee Dubois
Summary: The study found that infants with segmental facial or periorbital focal hemangiomas may have PHACES or similar syndrome regardless of the size of the hemangioma. Cerebrovascular and brain anomalies associated with PHACES syndrome are common, while cardiovascular and ocular anomalies are less common.
AMERICAN JOURNAL OF ROENTGENOLOGY
(2021)
Review
Dermatology
Young Wook Ko, Joo Yeon Ko, Young Suck Ro, Jeong Eun Kim
Summary: Oral-facial-digital syndrome type 1 (OFD1) is an X-linked dominant condition characterized by abnormalities in the face, oral cavity, and digits. This case report describes a rare case of OFD1 featuring congenital milia, which has not been previously reported in the Korean literature.
ANNALS OF DERMATOLOGY
(2022)
Article
Genetics & Heredity
Quentin Thomas, Antonio Vitobello, Frederic Tran Mau-Them, Yannis Duffourd, Agnes Fromont, Maurice Giroud, Benoit Daubail, Agnes Jacquin-Piques, Marie Hervieu-Begue, Thibault Moreau, Guy-Victor Osseby, Philippine Garret, Sophie Nambot, Julian Delanne, Ange-Line Bruel, Arthur Sorlin, Patrick Callier, Anne-Sophie Denomme-Pichon, Laurence Faivre, Yannick Bejot, Christophe Philippe, Christel Thauvin-Robinet, Sebastien Moutton
Summary: The study demonstrates that clinical exome sequencing (cES) is a powerful tool for daily neurogenetics practice offering an efficient (43%) and appropriate approach for clinically and genetically complex and heterogeneous disorders.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Annie Laquerriere, Dana Jaber, Emanuela Abiusi, Jerome Maluenda, Dan Mejlachowicz, Alexandre Vivanti, Klaus Dieterich, Radka Stoeva, Loic Quevarec, Flora Nolent, Valerie Biancalana, Philippe Latour, Damien Sternberg, Yline Capri, Alain Verloes, Bettina Bessieres, Laurence Loeuillet, Tania Attie-Bitach, Jelena Martinovic, Sophie Blesson, Florence Petit, Claire Beneteau, Sandra Whalen, Florent Marguet, Jerome Bouligand, Delphine Heron, Geraldine Viot, Jeanne Amiel, Daniel Amram, Celine Bellesme, Martine Bucourt, Laurence Faivre, Pierre-Simon Jouk, Suonavy Khung, Sabine Sigaudy, Anne-Lise Delezoide, Alice Goldenberg, Marie-Line Jacquemont, Laetitia Lambert, Valerie Layet, Stanislas Lyonnet, Arnold Munnich, Lionel Van Maldergem, Juliette Piard, Fabien Guimiot, Pierre Landrieu, Pascaline Letard, Fanny Pelluard, Laurence Perrin, Marie-Helene Saint-Frison, Haluk Topaloglu, Laetitia Trestard, Catherine Vincent-Delorme, Helge Amthor, Christine Barnerias, Alexandra Benachi, Eric Bieth, Elise Boucher, Valerie Cormier-Daire, Andree Delahaye-Duriez, Isabelle Desguerre, Bruno Eymard, Christine Francannet, Sarah Grotto, Didier Lacombe, Fanny Laffargue, Marine Legendre, Dominique Martin-Coignard, Andre Megarbane, Sandra Mercier, Mathilde Nizon, Luc Rigonnot, Fabienne Prieur, Chloe Quelin, Hanitra Ranjatoelina-Randrianaivo, Nicoletta Resta, Annick Toutain, Helene Verhelst, Marie Vincent, Estelle Colin, Catherine Fallet-Bianco, Michele Granier, Romulus Grigorescu, Julien Saada, Marie Gonzales, Anne Guiochon-Mantel, Jean-Louis Bessereau, Marcel Tawk, Ivo Gut, Cyril Gitiaux, Judith Melki
Summary: In this study, genetic diagnosis was achieved in 52.7% of AMC index patients, with the identification of nine newly discovered genes. The primary cause of AMC was determined to be skeletal muscle involvement (40%), with autosomal recessive inheritance being the most frequent mode (66.3%). In sporadic cases born to non-consanguineous parents, de novo dominant autosomal or X linked variants were observed in 50% of cases.
JOURNAL OF MEDICAL GENETICS
(2022)
Review
Genetics & Heredity
Nunziana Pezzella, Guglielmo Bove, Roberta Tammaro, Brunella Franco
Summary: The OFD1 protein is crucial for the formation of primary cilia and left-right asymmetry establishment and has additional functions. Mutations in OFD1 lead to various phenotypes with different inheritance patterns. The extensive clinical manifestations observed in OFD1-mutated patients highlight the complexity of genetic diseases.
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Ange-Line Bruel, Antonio Vitobello, Isabelle Thiffault, Linda Manwaring, Marcia Willing, Pankaj B. Agrawal, Allan Bayat, Thomas M. Kitzler, Catherine A. Brownstein, Casie A. Genetti, Joseph Gonzalez-Heydrich, Parul Jayakar, Jacob W. Zyskind, Zehua Zhu, Clemence Vachet, Gena R. Wilson, Brianna Pruniski, Anne-Marie Goyette, Yannis Duffourd, Christel Thauvin-Robinet, Christophe Philippe, Laurence Faivre
Summary: The study confirms the important role of the ITSN1 gene in neurodevelopmental disorders such as autism. Truncating variants and missense variants in ITSN1 exhibit different patterns and symptoms in affected patients.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Anne-Sophie Denomme-Pichon, Antonio Vitobello, Robert Olaso, Alban Ziegler, Mederic Jeanne, Frederic Tran Mau-Them, Victor Couturier, Caroline Racine, Bertrand Isidor, Charlotte Poe, Thibaud Jouan, Anne Boland, Bertrand Fin, Delphine Bacq-Daian, Celine Besse, Aurore Garde, Adeline Prost, Philippine Garret, Emilie Tisserant, Julian Delanne, Sophie Nambot, Aurelien Juven, Magali Gorce, Mathilde Nizon, Marie Vincent, Sebastien Moutton, Melanie Fradin, Alinoe Lavillaureix, Paul Rollier, Yline Capri, Julien Van-Gils, Tiffany Busa, Sabine Sigaudy, Laurent Pasquier, Magalie Barth, Ange-Line Bruel, Cyril Flamant, Clement Prouteau, Dominique Bonneau, Annick Toutain, Corinne Chantegret, Patrick Callier, Christophe Philippe, Yannis Duffourd, Jean-Francois Deleuze, Arthur Sorlin, Laurence Faivre, Christel Thauvin-Robinet
Summary: Accelerated trio-genome sequencing (GS) is valuable for infants with early-onset rare diseases in urgent care contexts, leading to molecular diagnosis with corrective measures and protocol adaptations. A circuit with rapid or ultra-rapid GS should coexist, with decreasing costs resulting in generalized use for diagnostic purposes and reduction of the costs of rapid GS.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Oncology
Edwige Kasper, Sophie Coutant, Sandrine Manase, Stephanie Vasseur, Pierre Macquere, Gaelle Bougeard, Laurence Faivre, Olivier Ingster, Stephanie Baert-Desurmont, Claude Houdayer
Summary: Inversions, a known cause of human diseases, are often overlooked. This study highlights the importance of inversion detection in routine diagnosis through case examples from two families.
Article
Genetics & Heredity
Flavien Rouxel, Raissa Relator, Jennifer Kerkhof, Haley McConkey, Michael Levy, Patricia Dias, Mouna Barat-Houari, Nathalie Bednarek, Odile Boute, Nicolas Chatron, Florian Cherik, Andree Delahaye-Duriez, Martine Doco-Fenzy, Laurence Faivre, Lucas W. Gauthier, Delphine Heron, Michael S. Hildebrand, Gaetan Lesca, James Lespinasse, Benoit Mazel, Leonie A. Menke, Angela T. Morgan, Lucile Pinson, Chloe Quelin, Massimiliano Rossi, Nathalie Ruiz-Pallares, Frederic Tran-Mau-Them, Imke N. Van Kessel, Marie Vincent, Mathys Weber, Marjolaine Willems, Gwenael Leguyader, Bekim Sadikovic, David Genevieve
Summary: This study reports the clinical features and genome-wide DNA methylation characterization of 18 novel individuals with CDK13-related disorder (CDK13-RD). The results reveal a global hypomethylated profile in CDK13-RD individuals and suggest the potential diagnostic utility of CDK13-RD DNA methylation episignature.
GENETICS IN MEDICINE
(2022)
Review
Genetics & Heredity
Juliette Coursimault, Anne-Marie Guerrot, Michelle M. Morrow, Catherine Schramm, Francisca Millan Zamora, Anita Shanmugham, Shuxi Liu, Fanggeng Zou, Frederic Bilan, Gwenael Le Guyader, Ange-Line Bruel, Anne-Sophie Denomme-Pichon, Laurence Faivre, Frederic Tran Mau-Them, Marine Tessarech, Estelle Colin, Salima El Chehadeh, Benedicte Gerard, Elise Schaefer, Benjamin Cogne, Bertrand Isidor, Mathilde Nizon, Diane Doummar, Stephanie Valence, Delphine Heron, Boris Keren, Cyril Mignot, Charles Coutton, Francoise Devillard, Anne-Sophie Alaix, Jeanne Amiel, Laurence Colleaux, Arnold Munnich, Karine Poirier, Marlene Rio, Sophie Rondeau, Giulia Barcia, Bert Callewaert, Annelies Dheedene, Candy Kumps, Sarah Vergult, Bjoern Menten, Wendy K. Chung, Rebecca Hernan, Austin Larson, Kelly Nori, Sarah Stewart, James Wheless, Christina Kresge, Beth A. Pletcher, Roseline Caumes, Thomas Smol, Sabine Sigaudy, Christine Coubes, Margaret Helm, Rosemarie Smith, Jennifer Morrison, Patricia G. Wheeler, Amy Kritzer, Guillaume Jouret, Alexandra Afenjar, Jean-Francois Deleuze, Robert Olaso, Anne Boland, Christine Poitou, Thierry Frebourg, Claude Houdayer, Pascale Saugier-Veber, Gael Nicolas, Francois Lecoquierre
Summary: Pathogenic variants of the MYT1L gene cause a syndromic neurodevelopmental disorder characterized by developmental delay, intellectual disability, overweight or obesity, behavioral disorders, and epilepsy. Additional clinical features include learning disabilities, feeding difficulties, and varied dysmorphic features. Highly clustered missense variants do not show significant clinical differences compared to truncating variants. This study provides updated clinical and genetic data for improved diagnosis and management of MYT1L-associated neurodevelopmental disorder patients.
Article
Genetics & Heredity
Smitha Kumble, Amanda M. Levy, Jaya Punetha, Hua Gao, Nicholas Ah Mew, Kwame Anyane-Yeboa, Paul J. Benke, Sara M. Berger, Lise Bjerglund, Belinda Campos-Xavier, Michael Ciliberto, Julie S. Cohen, Anne M. Comi, Cynthia Curry, Lena Damaj, Anne-Sophie Denomme-Pichon, Lisa Emrick, Laurence Faivre, Mary Beth Fasano, Alice Fievet, Richard S. Finkel, Sixto Garcia-Minaur, Amanda Gerard, Paulino Gomez-Puertas, Maria J. Guillen Sacoto, Trevor L. Hoffman, Lillian Howard, Alejandro D. Iglesias, Kosuke Izumi, Austin Larson, Anja Leiber, Reymundo Lozano, Inigo Marcos-Alcalde, Cassie S. Mintz, Sureni V. Mullegama, Rikke S. Moller, Sylvie Odent, Henry Oppermann, Elsebet Ostergaard, Marta Pacio-Miguez, Maria Palomares-Bralo, Sumit Parikh, Anna M. Paulson, Konrad Platzer, Jennifer E. Posey, Lorraine Potocki, Anya Revah-Politi, Marlene Rio, Alyssa L. Ritter, Scott Robinson, Jill A. Rosenfeld, Fernando Santos-Simarro, Sergio B. Sousa, Mathys Weber, Yili Xie, Wendy K. Chung, Natasha J. Brown, Zeynep Tumer
Summary: De novo variants in QRICH1 have been identified in individuals with intellectual disability, contributing to a neurodevelopmental disorder. The common clinical features include developmental delay, facial dysmorphism, and hypotonia, with additional findings of poor weight gain, short stature, autism spectrum disorder, seizures, and scoliosis. Some variants are inherited from mildly affected parents, suggesting variable expressivity.
Article
Pediatrics
Imke Anise Maartje Ditters, Hidde Harmen Huidekoper, Michelle Elisabeth Kruijshaar, Dimitris Rizopoulos, Andreas Hahn, Tiziana Enrico Mongini, Francois Labarthe, Marine Tardieu, Brigitte Chabrol, Anais Brassier, Rossella Parini, Giancarlo Parenti, Nadine Anna Maria Elisabeth van der Beek, Ans Tjitske van der Ploeg, Johanna Maria Pieternel van den Hout
Summary: This study assessed the effect of enzyme replacement therapy (ERT) with alglucosidase alfa on survival and walking ability in patients with classic infantile Pompe disease. The results showed that a high ERT dosage of 40 mg/kg per week significantly improved survival compared to the standard recommended dosage of 20 mg/kg every other week. These findings suggest a need for reconsideration of the currently registered dosage.
LANCET CHILD & ADOLESCENT HEALTH
(2022)
Review
Biochemistry & Molecular Biology
Manuela Morleo, Nunziana Pezzella, Brunella Franco
Summary: The balance of protein synthesis and degradation is crucial for cellular homeostasis and biological processes. Recent studies have revealed that centrosomal/ciliary proteins play a role in proteome control in response to spatial or microenvironmental stimuli. Understanding this balance in ciliopathies may lead to the identification of novel therapeutic targets for these genetic disorders.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Kishor Pant, Seth Richard, Estanislao Peixoto, Jun Yin, Davis M. Seelig, Pietro Carotenuto, Massimiliano Salati, Brunella Franco, Lewis R. Roberts, Sergio A. Gradilone
Summary: The study reveals that targeting the NAMPT/NAD+ pathway with FK866 can inhibit the growth of CCA cells and alter their mitochondrial metabolism. Additionally, FK866 enhances the anticancer effects of cisplatin in vitro. These findings suggest that NAMPT/NAD+ pathway may be a potential therapeutic target for CCA, and FK866 may serve as a useful medication in combination with cisplatin.
Review
Genetics & Heredity
Mina Kolahdouzmohammadi, Roya Kolahdouz-Mohammadi, Seyed Abdolhossein Tabatabaei, Brunella Franco, Mehdi Totonchi
Summary: Autophagy is a highly conserved biological process that controls intracellular recycling and is crucial for cellular homeostasis and differentiation programs, including cardiomyocyte differentiation. The interaction between autophagy and signaling pathways such as FGF, Wnt, Notch, and BMPs is essential for controlling cardiac differentiation. Modulating autophagy has been shown to improve cardiac differentiation and generate mature cardiac cells, highlighting the importance of further studying autophagy in this process.
Review
Genetics & Heredity
Pietro Carotenuto, Sergio A. Gradilone, Brunella Franco
Summary: Cilia are microtubule-based organelles that project from the cell surface with motility or sensory functions. The primary cilia work as antennae to sense and transduce extracellular signals. Recent studies have shown that primary cilia play important roles in autophagy and genome stability, which are crucial in oncogenesis.
Article
Genetics & Heredity
Michael A. Levy, Haley McConkey, Jennifer Kerkhof, Mouna Barat-Houari, Sara Bargiacchi, Elisa Biamino, Gerarda Cappuccio, Andrea Ciolfi, Angus Clarke, Barbara R. DuPont, Mariet W. Elting, Laurence Faivre, Timothy Fee, Robin S. Fletcher, Florian Cherik, Aidin Foroutan, Michael J. Friez, Cristina Gervasini, Sadegheh Haghshenas, Benjamin A. Hilton, Zandra Jenkins, Simranpreet Kaur, Suzanne Lewis, Raymond J. Louie, Silvia Maitz, Donatella Milani, Angela T. Morgan, Renske Oegema, Elsebet Ostergaard, Nathalie Ruiz Pallares, Maria Piccione, Simone Pizzi, Astrid S. Plomp, Cathryn Poulton, Jack Reilly, Raissa Relator, Rocio Rius, Stephen Robertson, Kathleen Rooney, Justine Rousseau, Gijs W. E. Santen, Fernando Santos-Simarro, Josephine Schijns, Gabriella Maria Squeo, Miya St John, Christel Thauvin-Robinet, Giovanna Traficante, Pleuntje J. van der Sluijs, Samantha A. Vergano, Niels Vos, Kellie K. Walden, Dimitar Azmanov, Tugce Balci, Siddharth Banka, Jozef Gecz, Peter Henneman, Jennifer A. Lee, Marcel M. A. M. Mannens, Tony Roscioli, Victoria Siu, David J. Amor, Gareth Baynam, Eric G. Bend, Kym Boycott, Nicola Brunetti-Pierri, Philippe M. Campeau, John Christodoulou, David Dyment, Natacha Esber, Jill A. Fahrner, Mark D. Fleming, David Genevieve, Kristin D. Kerrnohan, Alisdair McNeill, Leonie A. Menke, Giuseppe Merla, Paolo Prontera, Cheryl Rockman-Greenberg, Charles Schwartz, Steven A. Skinner, Roger E. Stevenson, Antonio Vitobello, Marco Tartaglia, Marielle Alders, Matthew L. Tedder, Bekim Sadikovic
Summary: Overlapping clinical phenotypes and complex genomic associations pose challenges in diagnosing and managing Mendelian disorders. This study identifies 19 new episignature disorders, in addition to 38 previously established episignatures, associated with a total of 65 genetic syndromes. The study demonstrates increasing resolution and specificity in identifying Mendelian episignatures at various molecular levels, and shows the development of accurate and disease-specific diagnostic classifiers. The findings expand the understanding of Mendelian conditions, improve clinical diagnostic capabilities, and offer potential reclassification of variants of unknown clinical significance.
HUMAN GENETICS AND GENOMICS ADVANCES
(2022)