Article
Biochemical Research Methods
Aojie Lian, James Guevara, Kun Xia, Jonathan Sebat
Summary: SynthDNM is a random-forest based classifier that can adapt to new sequencing or variant-calling pipelines by constructing simulated training examples from real data using a flexible approach. The optimized SynthDNM classifiers accurately predict de novo SNPs and indels across multiple variant calling methods.
Article
Biochemistry & Molecular Biology
Patryk Lipinski, Krzysztof Szczaluba, Piotr Buda, Ekaterina Y. Zakharova, Galina Baydakova, Agnieszka Lugowska, Agnieszka Rozdzynska-Swiatkowska, Zuzanna Cyske, Grzegorz Wegrzyn, Agnieszka Pollak, Rafal Ploski, Anna Tylki-Szymanska
Summary: This article reports a Polish MPS-PS patient with a novel VPS33A gene variant and new clinical features. Functional analysis revealed some related biomarkers, and comparison with other cases helped broaden understanding of the disease phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Zhuang-Zhuang Yuan, Xiao-Hui Xie, Heng Gu, Wei-Zhi Zhang, Yi-Qiao Hu, Yi-Feng Yang, Zhi-Ping Tan
Summary: This study identified a novel ACTL6A variant in a Chinese individual, expanding its role in heart, upper limb skeletal, and intellectual development. Mutation analysis of the ACTL6A gene can help avoid misdiagnosis in patients with BAF-opathies or heart-hand syndromes.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Pediatrics
Meifang Lei, Ping Wang, Hong Li, Xiaojun Liu, Jianbo Shu, Qianqian Zhang, Chunquan Cai, Dong Li, Yuqin Zhang
Summary: This study identified a novel variant of the TRPM7 gene in a patient with hemiplegic migraine attacks and hypomagnesemia. The findings highlight the importance of molecular genetic evaluation in patients with TRPM7 gene deficiency and demonstrate the causal relationship between TRPM7 gene variants and disease manifestations.
FRONTIERS IN PEDIATRICS
(2022)
Article
Biotechnology & Applied Microbiology
Marina Braun, Annika Lehmbecker, Deborah Eikelberg, Maren Hellige, Andreas Beineke, Julia Metzger, Ottmar Distl
Summary: A stillborn Limousin calf with severe craniofacial malformations, including absence of nose and maxilla, upwardly curved mandibles, median cleft palate, undeveloped eyes, optic nerve and orbital cavities, and a defect in the front skull covered with a membrane extending into the intracranial cavity, was found to have a private frameshift variant within the ZIC2 gene. This novel mutation in cattle is likely to have originated as a de novo mutation in the germline of one parent or during early embryonic development.
Article
Biochemistry & Molecular Biology
Jakob M. Goldmann, Juliet E. Hampstead, Wendy S. W. Wong, Amy B. Wilfert, Tychele N. Turner, Marianne A. Jonker, Raphael Bernier, Martijn A. Huynen, Evan E. Eichler, Joris A. Veltman, George L. Maxwell, Christian Gilissen
Summary: The number of de novo mutations in human germline is correlated with parental age, but only explains part of the variation. Family-specific contribution explains around 5.2% of the variation in DNM number, while stochasticity explains a large proportion of the variation in DNM counts.
Article
Biochemistry & Molecular Biology
Feda E. Mohamed, Amanat Ali, Amal Al-Tenaiji, Amina Al-Jasmi, Fatma Al-Jasmi
Summary: In this study, two Emirati families with Gaucher-like disorder due to Saposin C deficiency were reported. Molecular analysis revealed a novel splice site variant in the PSAP gene in these patients, resulting in the complete loss of Saposin C. Clinical examination showed a wide heterogeneity in age of onset and symptoms, expanding the genetic and clinical spectrum of Saposin C deficiency.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
S. Yimenicioglu, A. Kocaaga
Summary: This study reports the first case of Koolen-de Vries syndrome in Turkey, characterized by intellectual disability, developmental delay, epilepsy, and dysmorphic facial features. The genetic mutation in the KANSL1 gene was identified.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2022)
Article
Genetics & Heredity
Martin L. Katz, James Cook, Charles H. Vite, Rebecca S. Campbell, Lyndon M. Coghill, Leslie A. Lyons
Summary: This article describes a neurologic evaluation of a 6-month-old cat with progressive motor impairment. Whole genome sequence analysis identified a mutation in the MANBA gene that resulted in the loss of beta-mannosidase activity and caused beta-mannosidosis. Postmortem examination revealed significant accumulation of vacuolar inclusions in the cat's brain tissue.
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
Endocrinology & Metabolism
Otto Lennartsson, Maria Lodefalk, Henrik Wehtje, Eva-Lena Stattin, Lars Saevendahl, Ola Nilsson
Summary: This study presents a rare clinical case of a patient with Tatton-Brown-Rahman syndrome who underwent bilateral epiphysiodesis surgery for tall stature management. The surgery resulted in an increase in height, with a more modest increase in leg length.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Qiuyan Mai, Ruining Han, Yinlong Chen, Ke Shen, Shimin Wang, Qingliang Zheng
Summary: This study identified a novel de novo variant (c. 1309G>A, p. Gly437Ser) in the COL1A1 gene as a potential genetic cause for fetal osteogenesis imperfecta (OI). Bioinformatic analysis suggested that the variant may impact protein function, expanding the variation spectrum of OI.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Clinical Neurology
Audrey Riquet, Pierre Cleuziou, Valentine Floret, Francois Quesque, Sabine Defoort, Thomas Smol
Summary: This article reports a case of a two-month-old infant with a de novo pathogenic variation of CACNA1G who presented with paroxysmal tonic upgaze (PTU) associated with congenital ataxia and other periodic neurological manifestations. Detailed video documentations of PTU, paroxysmal torticollis, and ataxia in a patient with a CACNA1G mutation are provided, allowing a better understanding of the underlying mechanisms of PTU and suggesting potential new avenues for clinical treatments.
PEDIATRIC NEUROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Steven Erwood, Teija M. Bily, Jason Lequyer, Joyce Yan, Nitya Gulati, Reid A. Brewer, Liangchi Zhou, Laurence Pelletier, Evgueni A. Ivakine, Ronald D. Cohn
Summary: This study demonstrates the use of the CRISPR prime editing method for high-throughput variant classification and functional characterization. The results show that the method is efficient and accurate, and can be applied to other genes with appropriate cellular assays.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Gelana Khazeeva, Karolis Sablauskas, Bart van der Sanden, Wouter Steyaert, Michael Kwint, Dmitrijs Rots, Max Hinne, Marcel van Gerven, Helger Yntema, Lisenka Vissers, Christian Gilissen
Summary: DeNovoCNN is a new method that utilizes deep convolutional neural network to accurately identify De novo mutations in genetic disorders. Trained on a large dataset, DeNovoCNN excels in recall and precision, outperforming existing methods.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Clinical Neurology
Hengameh Shams, Xiaorong Shao, Adam Santaniello, Gina Kirkish, Adil Harroud, Qin Ma, Noriko Isobe, Catherine Schaefer, Jacob L. McCauley, Bruce A. C. Cree, Alessandro Didonna, Sergio E. Baranzini, Nikolaos A. Patsopoulos, Stephen L. Hauser, Lisa F. Barcellos, Roland G. Henry, Jorge R. Oksenberg
Summary: Polygenic inheritance plays a pivotal role in multiple sclerosis susceptibility. The development of polygenic risk scores (PRS) can assess disease status and severity, providing enhanced risk assessment and radiographic outcomes. This study indicates important associations of PRS with risk assessment and tissue injury outcomes, potentially informing targeted screening and prevention strategies.
Article
Biochemistry & Molecular Biology
Sarah Fazal, Matt C. Danzi, Andre B. P. van Kuilenburg, Selina Reich, Andreas Traschutz, Benjamin Bender, Rene Leen, Camilo Toro, Karen Usdin, Bruce Hayward, David R. Adams, Clara D. M. van Karnebeek, Carlos R. Ferreira, Precilla D'Sousa, Mustafa Tekin, Stephan Zuchner, Matthis Synofzik
Summary: This study demonstrates the importance of combining bioinformatics analysis with advanced technologies in order to effectively diagnose rare disorders. The discovery of repeat expansions in the glutaminase gene helps in understanding the causes of ataxia and developmental delay.
HUMAN MOLECULAR GENETICS
(2023)
Article
Genetics & Heredity
Rebecca Freeman, Adriana Noronha, Jeremy Woods
Summary: To address the challenges in diagnosing rare Mendelian disorders, a next generation phenotyping workflow was developed to study developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities (DEGCAGS). Human Phenotype Ontology (HPO) terms were extracted from patient records and sorted according to hierarchy. Co-occurrence matrix was used to identify cosegregating phenotypes. A quantitative narrative using violin plots was created to illustrate phenotypic data over time. The NGP approach provides objective and reproducible phenotypic data similar to NGS.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Kristen Wigby, Monia Hammer, Mari Tokita, Priyanka Patel, Marilyn C. C. Jones, Austin Larson, Frances Velez Bartolomei, Natalie Dykzeul, Anne Slavotinek, Tiffany Yip, Sara Bandres-Ciga, Brittany N. N. Simpson, Kristen Suhrie, Suma Shankar, Regan Veith, Jennifer Bragg, Cynthia Powell, Stephen F. F. Kingsmore, David Dimmock, Jill Maron, Jonathan Davis, Miguel Del Campo
Summary: The use of unbiased genomic sequencing in critically ill infants with rare diseases such as Kabuki syndrome (KS) can provide valuable insights. This study retrospectively reviewed medical records of infants diagnosed with KS through genome-wide sequencing. Analysis of genomic data identified common phenotypic features and resulted in changes in management. Early use of unbiased genome-wide sequencing enabled molecular diagnosis prior to clinical recognition, expanding the understanding of KS and its phenotypic spectrum.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Medicine, Research & Experimental
Sunyang Fu, Liwei Wang, Sungrim Moon, Nansu Zong, Huan He, Vikas Pejaver, Rose Relevo, Anita Walden, Melissa Haendel, Christopher G. Chute, Hongfang Liu
Summary: An increasing number of studies are using natural language processing (NLP) to extract clinical information from electronic health records (EHRs) for observational research. However, there is currently a lack of standardized reporting guidelines for NLP-assisted observational studies, which may lead to ambiguity, knowledge gaps, and reproducibility challenges. To address these issues, a scoping review was conducted to examine the reporting practices of NLP-assisted observational studies, revealing a high variation in reporting practices, including inconsistent use of references, variation in reporting location, and different levels of detail in NLP methodology and evaluation.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Endocrinology & Metabolism
Sangwoo T. Han, Ashley Hirt, Elena-Raluca Nicoli, Mari Kono, Camilo Toro, Richard L. Proia, Cynthia J. Tifft
Summary: Advances in gene therapy offer new possibilities for the treatment of monogenic disorders, and by analyzing the transcriptomes of fetal brain tissue, we have identified significant effects of TSD on brain development as well as changes in metabolic pathways. This study reveals the relationship between early pathology and gene expression, highlighting the importance of studying the pre-symptomatic stage.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Endocrinology & Metabolism
Elena-Raluca Nicoli, Mylene Huebecker, Sangwoo T. Han, Karolyn Garcia, Jeeva Munasinghe, Martin Lizak, Yvonne Latour, Robin Yoon, Brianna Glase, Michal Tyrlik, Morteza Peiravi, Danielle Springer, Eva H. Baker, David Priestman, Rohini Sidhu, Pamela Kell, Xuntian Jiang, Josephine Kolstad, Anna Luisa Kuhn, Mohammed Salman Shazeeb, Maria T. Acosta, Richard L. Proia, Frances M. Platt, Cynthia J. Tifft
Summary: Using CRISPR/Cas9 genome editing, a Glb1-/- mouse model was generated to evaluate characteristics of GM1 gangliosidosis. The model exhibited progressive abnormalities and cerebellar atrophy similar to patients, as well as increased levels of a novel biomarker and glycosphingolipid accumulation. This mouse model, despite being a null variant, most closely represents the less severe type II disease and will guide the development of new therapies.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Multidisciplinary Sciences
Alfred Jerrod Anzalone, Jing Sun, Amanda J. Vinson, William H. Beasley, William B. Hillegass, Kimberly Murray, Brian M. Hendricks, Melissa Haendel, Carol Reynolds Geary, Kristina L. Bailey, Corrine K. Hanson, Lucio Miele, Ronald Horswell, Julie A. McMurry, J. Zachary Porterfield, Michael T. Vest, H. Timothy Bunnell, Jeremy R. Harper, Bradley S. Price, Susan L. Santangelo, Clifford J. Rosen, James C. McClay, Sally L. Hodder
Summary: This study found that community factors impact the risk of breakthrough SARS-CoV-2 infections after vaccination, with higher risks observed in rural areas and counties with high vaccine hesitancy. It emphasizes the importance of targeting interventions and providing consistent guidance to these communities.
Article
Genetics & Heredity
Christina G. Tise, Courtney P. Verscaj, Bryce A. Mendelsohn, Jeremy Woods, Chung U. Lee, Gregory M. Enns, Zinandre Stander, Patricia L. Hall, Tina M. Cowan, Kristina P. Cusmano-Ozog
Summary: Low citrulline in newborn screening can be used to identify various mitochondrial diseases. This study found that infants with low citrulline were ultimately diagnosed with MT-ATP6 mitochondrial disease. By comparing with reference data, it is possible to effectively distinguish other types of diseases.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Carolina I. Galarreta, Karen Wong, Jason Carmichael, Jeremy Woods, Christina G. Tise, Annie D. Niehaus, Alison J. Schildt, Courtney P. Verscaj, Kristina P. Cusmano-Ozog
Summary: Zellweger spectrum disorder (ZSD) is a group of autosomal recessive disorders caused by biallelic pathogenic variants in any one of the 13 PEX genes essential for peroxisomal biogenesis. We report a cohort of nine infants who presented at birth with severe neonatal features suggestive of ZSD and found to be homozygous for a variant in PEX6 (NM_000287.4:c.1409G > C[p.Gly470Ala]). Gly470Ala may represent a founder variant in the Mixtec population of Central California. ZSD should be considered in patients who present at birth with severe hypotonia and enlarged fontanelles, especially in the setting of an abnormal NBS, Mixtec ancestry, or family history of infant death. There is a need to further characterize the natural history of ZSD, the Gly470Ala variant, and expand upon possible genotype-phenotype correlations.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Computer Science, Information Systems
Peter Leese, Adit Anand, Andrew Girvin, Amin Manna, Saaya Patel, Yun Jae Yoo, Rachel Wong, Melissa Haendel, Christopher G. Chute, Tellen Bennett, Janos Hajagos, Emily Pfaff, Richard Moffitt
Summary: This article presents a novel, generalizable method for resolving encounter heterogeneity for analysis by combining related atomic encounters into composite macrovisits, addressing the interpretability and usability issues of clinical encounter data.
JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
(2023)
Review
Genetics & Heredity
Marie Morimoto, Elena-Raluca Nicoli, Chulaluck Kuptanon, Joseph C. Roney, Jenny Serra-Vinardell, Prashant Sharma, David R. Adams, John Gallin, Steven M. Holland, Sergio D. Rosenzweig, Jose Barbot, Carla Ciccone, Marjan Huizing, Camilo Toro, William A. Gahl, Wendy J. Introne, May Christine Malicdan
Summary: The study identified 11 novel pathogenic LYST variants in patients with CHS, adding to a total of 147 variants in LYST. A genotype-phenotype correlation was observed, indicating that individuals with missense or in-frame variants usually have milder disease compared to those with nonsense or frameshift variants.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Shirley Nieves-Rodriguez, Florian Barthelemy, Jeremy D. Woods, Emilie D. Douine, Richard T. T. Wang, Deirdre D. Scripture-Adams, Kevin N. Chesmore, Francesca Galasso, M. Carrie Miceli, Stanley F. Nelson
Summary: Muscle damage and fibro-fatty replacement are key pathological features of Duchenne muscular dystrophy (DMD). This study investigated the differential gene expression between two skeletal muscles, vastus lateralis (VL) and tibialis anterior (TA), in healthy individuals, and identified potential mechanisms underlying the differential susceptibility of these muscles to DMD.
FRONTIERS IN GENETICS
(2023)
Article
Cardiac & Cardiovascular Systems
Christoffer Rasmus Vissing, Anna Axelsson Raja, Sharlene M. Day, Mark W. Russell, Kenneth Zahka, Harry M. Lever, Alexandre C. Pereira, Steven D. Colan, Renee Margossian, Anne M. Murphy, Charles Canter, Richard G. Bach, Matthew T. Wheeler, Joseph W. Rossano, Anjali T. Owens, Lee Benson, Luisa Mestroni, Matthew R. G. Taylor, Amit R. Patel, Ivan Wilmot, Philip Thrush, Jonathan H. Soslow, Jason R. Becker, Christine E. Seidman, Neal K. Lakdawala, Allison L. Cirino, John J. V. Mcmurray, Calum A. Macrae, Scott D. Solomon, Henning Bundgaard, E. John Orav, Carolyn Y. Ho
Summary: This study explored the potential of valsartan to modify disease development in subclinical HCM and characterized the short-term phenotypic progression. The results showed that valsartan did not have a significant effect on cardiac remodeling and the progression of subclinical HCM was minimal. Nearly one-fifth of the patients developed clinically overt HCM, and the transition to disease was associated with baseline interventricular septum thickness and left atrial volume index. These findings emphasize the importance of longitudinal follow-up of sarcomere variant carriers and the need to improve understanding of factors that drive disease penetrance and progression.
Article
Cell Biology
Jerry R. Mendell, Perry B. Shieh, Craig M. McDonald, Zarife Sahenk, Kelly J. Lehman, Linda P. Lowes, Natalie F. Reash, Megan A. Iammarino, Lindsay N. Alfano, Brenna Sabo, Jeremy D. Woods, Christy L. Skura, Howard C. Mao, Loretta A. Staudt, Danielle A. Griffin, Sarah Lewis, Shufang Wang, Rachael A. Potter, Teji Singh, Louise R. Rodino-Klapac
Summary: Delandistrogene moxeparvovec (SRP-9001) is a gene transfer therapy that effectively improves SRP-9001 dystrophin expression and shows promising results in patients with Duchenne muscular dystrophy. However, differences in baseline motor function between different age groups may confound the evaluation of treatment effectiveness.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)