Editorial Material
Medicine, Research & Experimental
Marjan Gucek, Michael N. Sack
Summary: By analyzing blood and urine samples from patients with MELAS syndrome, researchers have identified proteins and metabolites related to NADH-reductive stress, which may serve as important biomarkers for future management of the disease. These circulating biomarkers have intriguing clinical potential that could implicate disease pathophysiology and guide therapeutic efficacy monitoring.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Mahrou Sadri, Haichuan Wang, Toshinobu Kuroishi, Yong Li, Janos Zempleni
Summary: HLCS deficiency can lead to severe carboxylase deficiency, but early diagnosis and biotin treatment can prevent fatal consequences. This study successfully developed an HLCS conditional knockout mouse model and found that HLCS knockout has lethal effects on embryo survival.
Article
Multidisciplinary Sciences
Panayotis Pachnis, Zheng Wu, Brandon Faubert, Alpaslan Tasdogan, Wen Gu, Spencer Shelton, Ashley Solmonson, Aparna D. Rao, Akash K. Kaushik, Thomas J. Rogers, Jessalyn M. Ubellacker, Collette A. LaVigne, Chendong Yang, Bookyung Ko, Vijayashree Ramesh, Jessica Sudderth, Lauren G. Zacharias, Misty S. Martin-Sandoval, Duyen Do, Thomas P. Mathews, Zhiyu Zhao, Prashant Mishra, Sean J. Morrison, Ralph J. DeBerardinis
Summary: ETC activity regulates TCA cycle metabolism and C-13 labeling in tumors, indicating the involvement of multiple nutrients.
Article
Medicine, Research & Experimental
Manuela Lavorato, Eiko Nakamaru-Ogiso, Neal D. Mathew, Elizabeth Herman, Nina Shah, Suraiya Haroon, Rui Xiao, Christoph Seiler, Marni J. Falk
Summary: This study focuses on FBXL4(-/-) disease and identifies a potential therapeutic candidate, DCA, through the study of C. elegans and zebrafish animal models, as well as human fibroblasts. The study demonstrates the beneficial effects of DCA on fecundity, neurologic and/or muscular function, and mitochondrial physiology.
Article
Pediatrics
DongYing Tao, HuiQin Zhang, Jingmin Yang, HuanHong Niu, JingJing Zhang, Minghua Zeng, ShengQuan Cheng
Summary: The present study aimed to determine the effect of a novel homozygous splice-site variant in the pyruvate carboxylase (PC) gene on mRNA splicing. The study reported the clinical course of a 20-month-old Chinese pediatric patient diagnosed with pyruvate carboxylase deficiency (PCD) using whole-exome sequencing (WES). Transcript analysis in vivo indicated that the splice-site variant caused the retention of 192 bp of the intron.
FRONTIERS IN PEDIATRICS
(2022)
Article
Pediatrics
Francesco Baldo, Enrico Drago, Daniela Nistico, Silvia Buratti, Michaela Calvillo, Concetta Micalizzi, Maria Cristina Schiaffino, Mohamad Maghnie
Summary: This case describes a 5-year-old boy who developed severe lactic acidosis during the treatment for acute lymphoblastic leukemia. Thiamine deficiency caused by prolonged fasting and feeding difficulties led to the lactic acidosis, which was effectively treated with parenteral nutrition and thiamine supplementation.
Article
Medicine, General & Internal
Jessica Hidalgo, Leticia Campoverde, Juan Fernando Ortiz, Samir Ruxmohan, Ahmed Eissa-Garces
Summary: Pyruvate carboxylase deficiency is a rare inherited metabolic disorder characterized by movement disorders, neurologic disturbances, hypoglycemia, lactic acidosis, hyperammonemia, and elevated levels of pyruvate and alanine in plasma. The prognosis for PCD is poor, with most children dying within the first six months of life and survivors facing neurological damage and mental disability.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Endocrinology & Metabolism
Mei Xue
Summary: This case report describes the first case of type B pyruvate carboxylase deficiency in China. The patient presented with intractable lactic acidosis shortly after birth and prenatal neuroradiological presentations were observed. Despite treatment, the infant died at 26 days.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell & Tissue Engineering
Jingjing Sun, Pei Lu, Yunlin Shen, Li Ma
Summary: A new induced pluripotent stem cell line (SHCDNi007-A) was successfully generated from the peripheral blood mononuclear cells of a 2-month-old male infant with biallelic PC mutations, which is characterized by seizures, global developmental delay, lactic acidosis, and elevated plasma pyruvate and alanine levels. This cell line is expected to facilitate the in vitro modeling of the disease pathophysiology and the development of future therapeutics for PCD.
STEM CELL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Chynna N. Broxton, Prabhjot Kaur, Manuela Lavorato, Smruthi Ganesh, Rui Xiao, Neal D. Mathew, Eiko Nakamaru-Ogiso, Vernon E. Anderson, Marni J. Falk
Summary: Dihydrolipoamide dehydrogenase (DLD) deficiency is a genetic disorder caused by mitochondrial depletion. By studying the nematode Caenorhabditis elegans, researchers found that DLD-1 deficiency leads to increased mitochondrial stress and impaired growth and neuromuscular function. The potential therapeutic effects of dichloroacetate and thiamine were demonstrated in this study.
Article
Medicine, Research & Experimental
Nathaniel K. Mullin, Andrew P. Voigt, Miles J. Flamme-Wiese, Xiuying Liu, Megan J. Riker, Katayoun Varzavand, Edwin M. Stone, Budd A. Tucker, Robert F. Mullins
Summary: Variants in the high copy number mitochondrial genome can disrupt organelle function and lead to severe multisystem disease. Heteroplasmy, the uneven distribution of abnormal mtDNA molecules in different cells and tissues, contributes to the wide range of manifestations observed in patients with mitochondrial disease. This study reveals the nonrandom nature of mitochondrial variant distribution in human mitochondrial disease, highlighting its importance for understanding pathogenesis and developing treatments.
Article
Biochemistry & Molecular Biology
Samia Falak, Muhammad Sulaiman Saeed, Naeem Rashid
Summary: This manuscript describes the recombinant expression, characterization, and structural analysis of Pyrobaculum calidifontis' Pcal_0029 pyruvate kinase. The recombinant Pcal_0029 was produced in a soluble and highly active form. The purified protein exhibited metal-dependent activity and high thermostability. In silico structural analysis revealed eight conserved regions, and mutational studies showed substitutions that resulted in decreased enzyme activity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Medicine, General & Internal
Saima Sharif, Pradeep Kumar Velumula, Praveen Kumar Boddu, Deniz Altinok, Nithi Fernandes
Summary: This article describes a rare condition called pyruvate carboxylase (PC) enzyme deficiency, which is characterized by lactic acidosis and brain abnormalities. The diagnosis of PC enzyme deficiency was confirmed through biochemical evaluation, imaging, and molecular genetic analysis. The infant passed away on the 22nd day after birth.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2022)
Article
Medicine, Research & Experimental
Rohit Sharma, Bryn Reinstadler, Kristin Engelstad, Owen S. Skinner, Erin Stackowitz, Ronald G. Haller, Clary B. Clish, Kerry Pierce, Melissa A. Walker, Robert Fryer, Devin Oglesbee, Xiangling Mao, Dikoma C. Shungu, Ashok Khatri, Michio Hirano, Darryl C. De Vivo, Vamsi K. Mootha
Summary: This study identified 20 circulating markers that can distinguish patients with MELAS from controls, including both classic and recently identified mitochondrial markers. These markers correlate strongly with disease severity and are largely attributable to an elevated NADH/NAD(+) ratio.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Medicine, Research & Experimental
Youngran Park, Jin-Gyoung Jung, Zheng-Cheng Yu, Ryoichi Asaka, Wenjing Shen, Yeh Wang, Wei-Hung Jung, Alicja Tomaszewski, Geoff Shimberg, Yun Chen, Vamsi Parimi, Stephanie Gaillard, Ie-Ming Shih, Tian-Li Wang
Summary: The study introduces a new human endometrial epithelial cell line, hEM3, which is non-transformed, capable of stable in vitro growth, and can serve as a model for studying the pathogenesis of endometrium-related diseases.
LABORATORY INVESTIGATION
(2021)
Article
Dermatology
N. Bellon, S. Hadj-Rabia, F. Moulin, C. Lambe, G. Lezmi, F. Charbit-Henrion, C. Alby, L. Le Sache-de Peufeilhoux, S. Leclerc-Mercier, A. Hadchouel, J. Steffann, A. Hovnanian, A. Lapillonne, C. Bodemer
Summary: Netherton syndrome (NS) is a rare genetic disease with variable skin and hair involvement, often accompanied by allergic manifestations. Clinical management is challenging as patients have a high risk of metabolic anomalies and nutritional needs, especially in severe cases associated with specific gene mutations. Unexpected clinical complications may occur, emphasizing the importance of early detection and multidisciplinary management strategies to reduce the risk of mortality.
BRITISH JOURNAL OF DERMATOLOGY
(2021)
Article
Oncology
Marie-Charlotte Villy, Nelly Frydman, Celine Moutou, Gaelle Thierry, Jade Raad, Chrystelle Colas, Julie Steffann, Julie Metras, Nathalie Chabbert-Buffet, Yann Parc, Stephane Richard, Patrick R. Benusiglio
Summary: Data on preimplantation genetic testing (PGT-M) in patients with genetic susceptibility to cancer are scarce. A retrospective multicenter study was conducted to collect data on PGT-M outcomes and raise awareness among cancer genetics professionals. The study showed satisfactory PGT-M outcomes in patients with cancer susceptibility syndromes, highlighting the need for systematic counseling and increased awareness of PGT-M among cancer genetics professionals.
Article
Genetics & Heredity
Mathilde Weber, Dana Jaber, Ferechte Encha-Razavi, Emmanuel Julien, Julie Grevoul-Fesquet, Julie Steffann, Judith Melki, Jelena Martinovic
Summary: This study provides the first description of two fetal FADS cases carrying TUBA1A variants, broadening the phenotypic spectrum of TUBA1A variants. The neuropathology of these cases shows common features of tubulinopathies, with dysmorphism of the basal ganglia being the most characteristic sign.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Obstetrics & Gynecology
Manon Carles, Charlotte Sonigo, Olivier Binois, Laetitia Hesters, Julie Steffann, Serge Romana, Nelly Frydman, Anne Mayeur
Summary: This study aimed to evaluate the impact of performing a second biopsy during preimplantation genetic testing (PGT) on pregnancy outcomes. The results showed that a significant proportion of embryos remained genetically undiagnosed after the initial biopsy. Among these embryos, more than half were found to be healthy after a second biopsy. The transfer of these embryos resulted in a high clinical pregnancy rate and live birth rate. Therefore, performing a second biopsy can prevent the discarding of transferable embryos and improve the chances of successful pregnancy.
JOURNAL OF GYNECOLOGY OBSTETRICS AND HUMAN REPRODUCTION
(2022)
Article
Genetics & Heredity
Laura Fertitta, Fabienne Charbit-Henrion, Stephanie Leclerc-Mercier, Thao Nguyen-Khoa, Robert Baran, Caroline Alby, Julie Steffann, Isabelle Sermet-Gaudelus, Smail Hadj-Rabia
Summary: Bothnian palmoplantar keratoderma is a genetic skin disorder characterized by yellowish-white keratinization after water-immersion. It is caused by mutations in the AQP5 gene, leading to widened channels in the eccrine sweat glands and increased water movement, resulting in swelling and hyperhidrosis.
Review
Oncology
Lucie Laot, Charlotte Sonigo, Julie Nobre, Alexandra Benachi, Traicie Dervin, Lina El Moujahed, Anne Mayeur, Dominique Stoppa-Lyonnet, Julie Steffann, Michael Grynberg
Summary: BRCA carriers may have lower ovarian reserve, affecting the success rates of PGT and FP. Currently, there is a lack of international guidelines for the application of PGT and FP in this subgroup of patients. This article aims to determine the actual indication of PGT and improve patients' care pathway by reviewing available data.
Article
Biology
Cerane Cafournet, Sofia Zanin, Anne Guimier, Marie Hully, Zahra Assouline, Giulia Barcia, Pascale de Lonlay, Julie Steffann, Arnold Munnich, Jean-Paul Bonnefont, Agnes Rotig, Benedetta Ruzzenente, Metodi D. Metodiev
Summary: Transcription of mitochondrial DNA involves the cleavage of long polycistronic precursors to yield individual mtDNA-encoded transcripts. Variants in the ELAC2 gene have been associated with cardiomyopathy and neurological presentations. This study reports on five patients with ELAC2-linked disease, some presenting with cardiomyopathy and varying neurological symptoms. Enzymatic and immunoblot analyses provide further insights into the molecular mechanisms behind this pathology.
Article
Obstetrics & Gynecology
Kalliopi Chatzovoulou, Anne Mayeur, Nicolas Cagnard, Mohammed Zarhrate, Christine Bole, Patrick Nitschke, Fabienne Jabot-Hanin, Agnes Rotig, Sophie Monnot, Arnold Munnich, Nelly Frydman, Julie Steffann
Summary: The presence of pathogenic mitochondrial variants leads to changes in gene expression in preimplantation human embryos, affecting their development, cell differentiation, and survival. Mitochondrial DNA anomalies have been linked to impaired human embryonic development, but the underlying mechanisms are still unknown.
HUMAN REPRODUCTION
(2023)
Meeting Abstract
Obstetrics & Gynecology
A. Mayeur, V. Vaucoret, F. Magnan, J. Steffann, J. Benguigui, C. Duperier, S. Monnot, A. Benachi, N. Frydman, M. Grynberg, C. Sonigo
HUMAN REPRODUCTION
(2022)
Meeting Abstract
Obstetrics & Gynecology
C. Sonigo, N. Ranisavljevic, M. Guigui, T. Anahory, A. Mayeur, C. Moutou, C. Rongieres, A. Reignier, T. Lefebvre, A. Girardet, P. Ray, J. Steffann, O. Pirrello, M. Grynberg
HUMAN REPRODUCTION
(2022)
Meeting Abstract
Obstetrics & Gynecology
K. Chatzovoulou, A. Mayeur, N. Cagnard, Z. Mohammed, C. Bole, P. Nitschke, F. Jabot-Hanin, A. Rotig, S. Monnot, J. P. Bonnefont, A. Munnich, N. Achour, J. Steffann
HUMAN REPRODUCTION
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Caroline Michot, Pauline Marzin, Genevieve Baujat, Coralie Haudry, Anne-Laure Tourre, Julie Steffann, Sophie Rondeau, Valerie Cormier-Daire
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Giulia Barcia, Marlene Rio, Zahra Assouline, Coralie Zangarelli, Charles-Joris Roux, Pascale de Lonlay, Julie Steffann, Isabelle Desguerre, Arnold Munnich, Jean-Paul Bonnefont, Nathalie Boddaert, Agnes Rotig, Metodi D. Metodiev, Benedetta Ruzzenente
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Genevieve Baujat, Roxana Borghese, Pascale Sonigo, Joana Bengoa, Caroline Michot, Elodie Millischer-Bellaiche, Sophie Rondeau, Beatrice Childs, Tania Attie-Bitach, Bettina Bessieres, Laurent Salomon, Yves Ville, Jean-Paul Bonnefont, Julie Steffann, Valerie Cormier-Daire
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Kalliopi Chatzovoulou, Anne Mayeur, Nadine Gigarel, Fabienne Jabot-Hanin, Laetitia Hesters, Arnold Munnich, Nelly Frydman, Jean-Paul Bonnefont, Julie Steffann
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)