Editorial Material
Cardiac & Cardiovascular Systems
Philipp Angleitner, Michael A. Arnoldner, Andreas O. Zuckermann, Arezu Z. Aliabadi-Zuckermann
Summary: Gastroparesis is a rare but severe complication after heart transplantation, which can lead to vomiting, aspiration, pneumonia, and altered pharmacokinetics of immunosuppressive medication with increased risk of severe side effects. A successful diagnostic and therapeutic strategy was described for managing gastroparesis in a patient.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2021)
Article
Cell Biology
Bokai Zhang, Xi Yang, Ming Li
Summary: Three recent studies have identified LYSET/TMEM251/GCAF as a key regulator of the M6P biosynthetic pathway. LYSET/TMEM251 interacts with GNPT, the enzyme responsible for M6P transfer, and is crucial for its activity and stability. Deletion of LYSET/TMEM251 impairs GNPT function and M6P modifications, resulting in mistargeting of lysosomal enzymes and the development of a lysosomal storage disease.
Article
Endocrinology & Metabolism
Georgianne L. Arnold, Jessie Yester, Elizabeth McCracken, Brian D. Feingold, Jerry Vockley
Summary: Carnitine palmitoyl transferase II (CPT II) deficiency can lead to a range of symptoms, including hypoglycemia, hyperammonemia, cardiomyopathy, and rhabdomyolysis. A severe case of infantile onset cardiomyopathy due to CPT II deficiency was successfully treated with orthotopic heart transplantation, demonstrating the feasibility of this management option for patients with severe forms of long chain fatty acid oxidation disorders.
MOLECULAR GENETICS AND METABOLISM
(2021)
Review
Cell Biology
Myeong Uk Kuk, Yun Haeng Lee, Jae Won Kim, Su Young Hwang, Joon Tae Park, Sang Chul Park
Summary: Lysosomal storage disease (LSD) is a genetic metabolic disorder with no effective treatment to restore normal levels. The crosstalk between lysosomes and mitochondria is crucial for cellular homeostasis, and the deficiency of lysosome enzymes in LSD leads to deterioration of the mitochondrial respiratory chain.
Review
Biochemistry & Molecular Biology
Rebecca Maechtel, Fanni Annamaria Boros, Jan Philipp Dobert, Philipp Arnold, Friederike Zunke
Summary: Lysosomes are acidic organelles responsible for recycling cellular components and can cause lysosomal dysfunction and LSDs when there is reduced enzymatic activity. Neurons are particularly susceptible to lysosomal dysfunction, leading to neurological symptoms. There are genetic associations between LSDs and Parkinson's disease, indicating common cellular mechanisms.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Rodrigo Canibano-Fraile, Laurike Harlaar, Carlos A. dos Santos, Marianne Hoogeveen-Westerveld, Jeroen A. A. Demmers, Tim Snijders, Philip Lijnzaad, Robert M. Verdijk, Nadine A. M. E. van der Beek, Pieter A. van Doorn, Ans T. van der Ploeg, Esther Brusse, W. W. M. Pim Pijnappel, Gerben J. Schaaf
Summary: Pompe disease is an inherited metabolic myopathy characterized by lysosomal glycogen accumulation caused by deficiency of acid alpha-glucosidase (GAA). This study found elevated protein levels of enzymes involved in glucose uptake and cytoplasmic glycogen synthesis in skeletal muscle of Pompe disease mice and patients. These metabolic changes occur before muscle wasting and may aggravate the disease phenotype.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Surgery
George H. B. Greenhall, Maria Ibrahim, Utkarsh Dutta, Carolyn Doree, Susan J. Brunskill, Rachel J. Johnson, Laurie A. Tomlinson, Chris J. Callaghan, Christopher J. E. Watson
Summary: Donor-transmitted cancer has significant implications for organ recipients, particularly in orthotopic transplants. While re-transplantation offers the best chance of cure, there is still a risk of tumor recurrence. Our findings suggest the need for improvements in clinical practice to address this issue.
TRANSPLANT INTERNATIONAL
(2022)
Review
Cardiac & Cardiovascular Systems
Haiwen Li, Lingqiang Zhang, Lei Zhang, Renzhi Han
Summary: This article summarizes the link between autophagy and cardiac and skeletal muscle defects, as well as discusses potential interventions to regulate autophagy activities in treating muscle diseases.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Maria A. Restrepo-Cordoba, Karim Wahbi, Anca R. Florian, Juan Jimenez-Jaimez, Luisa Politano, Michael Arad, Vicente Climent-Paya, Ana Garcia-Alvarez, Rasmus B. Hansen, Jose M. Larranaga-Moreira, Milos Kubanek, Luis R. Lopes, Andrea Ros, Ruxandra Jurcut, Torsten B. Rasmussen, Luis Ruiz-Guerrero, Regina Pribe-Wolferts, Julian Palomino-Doza, Zofia Bilinska, Jose F. Rodriguez-Palomares, Rosa L. E. Van Loon, Maria Teresa Basurte Elorz, Giovanni Quarta, Maria Robledo Inarritu, Job A. J. Verdonschot, Tanya Stojkovic, Zornitsa Shomanova, Francisco Bermudez-Jimenez, Alberto Palladino, Dov Freimark, Maria I. Garcia-alvarez, Paloma Jorda, Fernando Dominguez, Juan Pablo Ochoa, Francesca Girolami, Ramon Brugada, Benjamin Meder, Roberto Barriales-Villa, Jens Mogensen, Pascal Laforet, Ali Yilmaz, Perry Elliott, Pablo Garcia-Pavia
Summary: DMD-associated DCM in individuals without severe skeletal myopathy is characterized by incomplete penetrance, high risk of MACE, and similar survival regardless of the presence of skeletal myopathy. Onset of DCM is a major determinant of prognosis, with decreased LVEF and increased left ventricular end-diastolic diameter associated with MACE. Individuals without DCM have a favorable prognosis during follow-up.
EUROPEAN JOURNAL OF HEART FAILURE
(2021)
Article
Cardiac & Cardiovascular Systems
Nicholas R. Hess, Gavin W. Hickey, Ibrahim Sultan, Arman Kilic
Summary: The study investigated the trends, outcomes, and risk factors for mortality after redo orthotopic heart transplantation. The analysis included 40,711 recipients, with 97.4% undergoing primary transplantation and 2.6% undergoing redo transplantation. The study found that redo recipients had lower survival rates compared to primary recipients, and factors such as increasing donor age and graft ischemic times, along with pretransplant mechanical ventilation and blood transfusion, negatively affected survival.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2023)
Review
Endocrinology & Metabolism
Edouard Berling, Pascal Laforet, Karim Wahbi, Philippe Labrune, Francois Petit, Giuseppe Ronzitti, Alan O'Brien
Summary: GSDIII is a rare genetic metabolic disorder primarily affecting the liver, heart, and skeletal muscle. While it presents with hepatomegaly and growth delay in children, other heart and muscle issues should be considered in adults. In addition to discussing the pathophysiology and treatment strategies, new findings related to cardiac and neuromuscular impairment are also highlighted.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Daniela Tavian, Lorenzo Maggi, Marina Mora, Lucia Morandi, Cinzia Bragato, Sara Missaglia
Summary: Neutral lipid storage disease with myopathy (NLSDM) is a rare autosomal recessive disorder caused by enzymatic errors in lipid metabolism. It is characterized by skeletal muscle myopathy, variable cardiac and hepatic involvement, with mutations in the PNPLA2 gene being the underlying cause. Clinical presentation often includes early onset muscle weakness, particularly in the upper limbs, with a slowly evolving course over time.
Article
Medicine, General & Internal
Vivek Bhat, Ganaraja Harikrishna, Hyndav Kumar, Suresha Kodapala
Summary: This article reports a case of a 21-year-old male with dropped head syndrome, presenting with difficulty swallowing and inability to keep his head erect. Whole exome sequencing identified a hemizygous stop gain variant in the LAMP-2 gene, leading to a diagnosis of Danon disease. The management involves regular cardiac monitoring, physical therapy, and multidisciplinary treatment.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Adam J. Kanack, Kazuhiro Aoki, Michael Tiemeyer, Nancy M. Dahms
Summary: Fabry disease is caused by a deficiency of the lysosomal enzyme alpha-Galactosidase-A, leading to the accumulation of alpha-Gal A substrates and increased risk of thrombotic events. Studies in a rat model found that alpha-Gal A-deficient rats accumulate myeloid-derived leukocytes and megakaryocytes, increased levels of pro-inflammatory cytokines, and platelets with elevated binding ability to fibrinogen.
Article
Multidisciplinary Sciences
Kristina Fredriksen, Stefanos Aivazidis, Karan Sharma, Kevin J. Burbidge, Caleb Pitcairn, Friederike Zunke, Eilrayna Gelyana, Joseph R. Mazzulli
Summary: GBA1 mutations that encode lysosomal beta-glucocerebrosidase (GCase) cause Gaucher disease and are risk factors for synucleinopathies. The study found that alpha-synuclein neuropathology induced by GCase depletion depends on neuronal maturity, alpha-synuclein physiology, and specific accumulation of long-chain glycosphingolipid substrates. Reduction of long-chain glycosphingolipids can ameliorate alpha-synuclein pathology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Laurel Truscott, Joanna Gell, Vivian Y. Chang, Hane Lee, Samuel P. Strom, Rex Pillai, Anthony Sisk, Julian A. Martinez-Agosto, Martin Anderson, Noah Federman
PEDIATRIC BLOOD & CANCER
(2017)
Article
Genetics & Heredity
Paul C. Marcogliese, Vandana Shashi, Rebecca C. Spillmann, Nicholas Stong, Jill A. Rosenfeld, Mary Kay Koenig, Julian A. Martinez-Agosto, Matthew Herzog, Agnes H. Chen, Patricia I. Dickson, Henry J. Lin, Moin U. Vera, Noriko Salamon, Damara Ortiz, Elena Infante, Wouter Steyaert, Bart Dermaut, Bruce Poppe, Hyung-Lok Chung, Zhongyuan Zuo, Pei-Tseng Lee, Oguz Kanca, Fan Xia, Yaping Yang, Edward C. Smith, Joan Jasien, Sujay Kansagra, Gail Spiridigliozzi, Mays El-Dairi, Robert Lark, Kacie Riley, Dwight D. Koeberl, Katie Golden-Grant, Shinya Yamamoto, Michael F. Wangler, Ghayda Mirzaa, Dimitri Hemelsoet, Brendan Lee, Stanley F. Nelson, David B. Goldstein, Hugo J. Bellen, Loren D. M. Pena
AMERICAN JOURNAL OF HUMAN GENETICS
(2018)
Article
Genetics & Heredity
Sureni V. Mullegama, Steven D. Klein, Rebecca H. Signer, Eric Vilain, Julian A. Martinez-Agosto
MOLECULAR GENETICS & GENOMIC MEDICINE
(2019)
Article
Genetics & Heredity
Brian D. Friend, Kami Wolfe Schneider, Timothy Garrington, Laurel Truscott, Julian A. Martinez-Agosto, Robert S. Venick, Eileen Tsai Chambers, Patricia Weng, Douglas G. Farmer, Vivian Y. Chang, Noah Federman
MOLECULAR GENETICS & GENOMIC MEDICINE
(2019)
Article
Genetics & Heredity
Steven D. Klein, Dzung C. Nguyen, Viraj Bhakta, Derek Wong, Vivian Y. Chang, Tom B. Davidson, Julian A. Martinez-Agosto
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2019)
Article
Behavioral Sciences
Aaron D. Besterman, Joshua Sadik, Michael J. Enenbach, Fabiola Quintero-Rivera, Mark DeAntonio, Julian A. Martinez-Agosto
Article
Genetics & Heredity
Nathan Kopp, Ina Amarillo, Julian Martinez-Agosto, Fabiola Quintero-Rivera
Summary: NLGN4X is an X-linked postsynaptic scaffolding protein associated with neuropsychiatric disorders. A female proband with NLGN4X microdeletion inherited from her father showed ASD, while her father exhibited psychiatric phenotypes. This case provides further evidence that NLGN4X is sensitive to dosage changes in females.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Emily K. Mis, Annalisa G. Sega, Rebecca H. Signer, Tracy Cartwright, Weizhen Ji, Julian A. Martinez-Agosto, Stanley F. Nelson, Christina G. S. Palmer, Hane Lee, Thomas Mitzelfelt, Monica Konstantino, Lauren Jeffries, Mustafa K. Khokha, Elysa Marco, Martin G. Martin, Saquib A. Lakhani
Summary: A novel de novo heterozygous NEUROD2 missense variant was found in an adolescent with developmental delay but without seizures, displaying minimal protein activity in functional testing. Another rare NEUROD2 variant identified in an adolescent with developmental delay showed normal NEUROD2 activity, suggesting that NEUROD2 variants can lead to developmental delay without early-onset seizures.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Fabiola Quintero-Rivera, Celeste C. Eno, Christine Sutanto, Kelly L. Jones, Malgorzata J. M. Nowaczyk, Derek Wong, Dawn Earl, Ghayda Mirzaa, Anita Beck, Julian A. Martinez-Agosto
Summary: NSD1 plays a critical role in microduplication 5q35 syndrome, potentially affecting growth and psychiatric phenotypes by altering mTOR pathway signaling. The study also suggests that leucine supplementation may serve as a potential therapeutic approach to ameliorate the symptoms.
Article
Genetics & Heredity
Celeste C. Eno, Jesper Graakjaer, Dea Svaneby, Mathilde Nizon, Jessica Kianmahd, Rebecca Signer, Julian A. Martinez-Agosto, Fabiola Quintero-Rivera
Summary: Three unrelated patients have similar microdeletions of chromosome 14q32.11 with shared phenotypes, including language and developmental delay. Four overlapping genes in the deletion region are expressed in the brain and have haploinsufficiency scores, suggesting a potential influence on the resulting phenotype. This microdeletion may be associated with developmental and language delay based on the lack of normal variation in this region and the patients' similar phenotypes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Thomas W. Frazier, Ritika Jaini, Robyn M. Busch, Matthew Wolf, Tammy Sadler, Patricia Klaas, Antonio Y. Hardan, Julian A. Martinez-Agosto, Mustafa Sahin, Charis Eng
Summary: This study investigated differences in PTEN pathway protein levels in PTEN-ASD, PTEN no-ASD, and macro-ASD patients, and the associations between these protein levels and neurobehavioral functions. Results showed decreased levels of PTEN and S6 in PTEN mutation groups, while reductions in MnSOD and increases in P-S6 were observed in ASD groups. The study suggests that molecular measures contribute significantly to predicting neurobehavioral outcomes.
Article
Genetics & Heredity
Mirko Uljarevic, Thomas W. Frazier, Gaelle Rached, Robyn M. Busch, Patricia Klaas, Siddharth Srivastava, Julian A. Martinez-Agosto, Mustafa Sahin, Charis Eng, Antonio Y. Hardan
Summary: This study provides a comprehensive characterization of distinct RRB domains in individuals with PTEN mutations. Significant group differences were found in RMB, IS, and CI scales, with the PTEN-No ASD group showing lower scores compared to PTEN-ASD and Macro-ASD groups. Despite limitations, important assessment and treatment implications were highlighted in this investigation.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Yue Huang, Katheryn Grand, Virginia Kimonis, Merlin G. Butler, Suparna Jain, Alden Yen-Wen Huang, Julian A. Martinez-Agosto, Stanley F. Nelson, Pedro A. Sanchez-Lara
Summary: The study reports the first case of PWS associated with a de novo mosaic nonsense variant of the SNRPN gene, suggesting that gene sequencing should be considered in patients with clinical suspicion of PWS.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Cell Biology
Jamie Lee, Joshua Zhang, Maeve Flanagan, Julian A. Martinez, Christopher Cunniff, Nicole Kucine, Ake T. Lu, Amin Haghani, Juozas Gordevicius, Steve Horvath, Vivian Y. Chang
Summary: Bloom syndrome (BSyn) is caused by variants in the BLM gene and manifests as poor growth, sun sensitivity, mild immunodeficiency, diabetes, and increased cancer risk, particularly leukemias. Our study reveals accelerated epigenetic aging in BSyn patients compared to carriers, as evidenced by multiple measures in blood lymphocytes. Additionally, homozygous Blm mice exhibit accelerated methylation age in various tissues according to the brain methylation clock. Overall, Bloom syndrome is associated with accelerated epigenetic aging effects in multiple tissues and significant impact on CpG methylation levels.
Article
Biotechnology & Applied Microbiology
Ryan L. Collins, Harrison Brand, Claire E. Redin, Carrie Hanscom, Caroline Antolik, Matthew R. Stone, Joseph T. Glessner, Tamara Mason, Giulia Pregno, Naghmeh Dorrani, Giorgia Mandrile, Daniela Giachino, Danielle Perrin, Cole Walsh, Michelle Cipicchio, Maura Costello, Alexei Stortchevoi, Joon-Yong An, Benjamin B. Currall, Catarina M. Seabra, Ashok Ragavendran, Lauren Margolin, Julian A. Martinez-Agosto, Diane Lucente, Brynn Levy, Stephan J. Sanders, Ronald J. Wapner, Fabiola Quintero-Rivera, Wigard Kloosterman, Michael E. Talkowski