Article
Pediatrics
Guido Filler, Olivia Tremblay, Emily Chen, Susan Shi Han Huang, Robert Stein
Summary: This retrospective cohort study found that male patients with X-linked hypophosphataemic rickets (XLH) require higher doses of burosumab to achieve normal serum phosphate levels, while female patients show normalization of phosphate and alkaline phosphatase at the recommended dose.
PEDIATRIC NEPHROLOGY
(2023)
Article
Genetics & Heredity
Xiang Chen, Libing Yun, Yang Long, Yuxia Sun, Tao Chen
Summary: This study presents the first report of monozygotic twins with discordant phenotypes for NDI caused by a missense variant in the AVPR2 gene. Experimental evidence suggests that this variation is pathogenic. The study also suggests that the development of NDI symptoms is more closely associated with the XCI pattern in urine sediments compared with the XCI pattern in peripheral leukocytes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Jonathan Rodgers, Sophie Calvert, Cheryl Shoubridge, Julie McGaughran
Summary: Pathogenic variants in the ARX gene can lead to a variety of phenotypes, with intellectual disability being a common feature. We report a case of monozygotic female twins with a newly identified ARX variant, showing developmental delay and seizures, with one twin exhibiting more severe symptoms and developing chorea, a movement disorder rarely seen in ARX variants.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Patrycja Juchniewicz, Ewa Piotrowska, Anna Kloska, Magdalena Podlacha, Jagoda Mantej, Grzegorz Wegrzyn, Stefan Tukaj, Joanna Jakobkiewicz-Banecka
Summary: Advancements in genomic and metabolomic technologies are rapidly increasing our understanding of the molecular and biochemical causes of genetic disorders, with an emphasis on the varying phenotypes. Dosage compensation through lyonization helps balance gene expression on heteromorphic sex chromosomes, greatly impacting the manifestation of X-linked disorders in females. This review summarizes clinical and genetic findings in female carriers of pathogenic variants in selected X-linked genes that result in metabolic disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Francisco Bustos, Carmen Espejo-Serrano, Anna Segarra-Fas, Rachel Toth, Alison J. Eaton, Kristin D. Kernohan, Meredith J. Wilson, Lisa G. Riley, Greg M. Findlay
Summary: TOKAS is an X-linked intellectual disability syndrome caused by variants in the gene encoding RLIM. A novel missense variant in RLIM disrupts protein expression and function, leading to a severe form of the syndrome. This variant impairs E3 ubiquitin ligase activity and disrupts X-chromosome inactivation.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
Carmine Pecoraro, Tiziana Fioretti, Assunta Perruno, Antonella Klain, Daniela Cioffi, Adelaide Ambrosio, Diego Passaro, Luigi Annicchiarico Petruzzelli, Carmela Di Domenico, Domenico de Girolamo, Sabrina Vallone, Fabio Cattaneo, Rosario Ammendola, Gabriella Esposito
Summary: This study reports the clinical and genetic features of two Italian female infants with rare inherited hypophosphatemic rickets who responded well to burosumab treatment. Analysis revealed that large intragenic deletions in the PHEX gene could be a significant cause of X-linked dominant hypophosphataemia. These findings highlight the importance of evaluating deletions in PHEX among female patients with negative small nucleotide variants.
Article
Oncology
Sayaka Kawashima, Atsushi Hattori, Erina Suzuki, Keiko Matsubara, Machiko Toki, Rika Kosaki, Yukihiro Hasegawa, Kazuhiko Nakabayashi, Maki Fukami, Masayo Kagami
Summary: Research indicates that X-chromosome rearrangements generally do not impact the methylation status of escape gene promoters, except in cases of highly complex rearrangements involving the deletion of the FIRRE gene and the duplication of the DXZ4 gene.
CLINICAL EPIGENETICS
(2021)
Article
Genetics & Heredity
Hakon Jonsson, Erna Magnusdottir, Hannes P. Eggertsson, Olafur A. Stefansson, Gudny A. Arnadottir, Ogmundur Eiriksson, Florian Zink, Einar A. Helgason, Ingileif Jonsdottir, Arnaldur Gylfason, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Doruk Beyter, Thora Steingrimsdottir, Gudmundur L. Norddahl, Olafur Th. Magnusson, Gisli Masson, Bjarni V. Halldorsson, Unnur Thorsteinsdottir, Agnar Helgason, Patrick Sulem, Daniel F. Gudbjartsson, Kari Stefansson
Summary: Despite the significant role of monozygotic twins in genetics research, little is known about their genomic differences. This study found that on average monozygotic twins have 5.2 early developmental mutations, with approximately 15% of twins having a substantial number of unique early developmental mutations. The allocation of cells during development shapes the genomic differences between monozygotic twins.
Article
Multidisciplinary Sciences
Serena F. Generoso, Maria Victoria Neguembor, Elliot A. Hershberg, Ruslan I. Sadreyev, Kazuki Kurimoto, Yukihiro Yabuta, Raffaele Ricci, Pauline Audergon, Moritz Bauer, Mitinori Saitou, Konrad Hochedlinger, Brian J. Beliveau, Maria Pia Cosma, Jeannie T. Lee, Bernhard Payer
Summary: Reactivation of the inactive X chromosome is a key event during reprogramming, and the cohesin complex member SMC1a plays a crucial role in this process. Depletion of SMC1a affects X chromosome reactivation without interfering with iPSC-reprogramming, and it is necessary for the decompacted state of the active X chromosome. Our findings highlight the importance of cohesin in the remodeling of the X chromosome and its critical role in iPSC-reprogramming.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Cell Biology
Wenlun Wang, Lu Min, Xinyuan Qiu, Xiaomin Wu, Chuanyang Liu, Jiaxin Ma, Dongyi Zhang, Lingyun Zhu
Summary: Long non-coding RNAs (lncRNAs) play important roles in cellular functions by regulating target gene expression levels through epigenomic, transcriptional, and post-transcriptional approaches. Among them, long non-coding RNA X-inactive specific transcript (lncRNA Xist) acts as a crucial regulator in X chromosome inactivation and various disease processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eduardo Carrillo-Tapia, Sara E. Espinosa-Padilla, Daniela Perez-Perez, Maria E. Gonzalez-Serrano, Laura Berron-Ruiz, Francisco J. Espinosa-Rosales, Juan C. Rodriguez-Alba, Fabiola Mujica-Guzman, Emiy Yokoyama-Rebollar, Jose R. Garcia-Flores, Norma E. Herrera-Gonzalez, Selma Scheffler-Mendoza, Marco A. Yamazaki-Nakashimada, A. Tamara Staines-Boone, Gabriela Lopez-Herrera
Summary: Analysis of 30 potential carriers using modified HUMARA revealed successful determination of carrier status in most samples. B cell enrichment provided precise carrier determination data, reduced sample size, and facilitated identification of inactive and active alleles.
GENETIC TESTING AND MOLECULAR BIOMARKERS
(2022)
Article
Biology
Andrea Cerase, Alexander N. Young, Nerea Blanes Ruiz, Andreas Buness, Gabrielle M. Sant, Mirjam Arnold, Monica Di Giacomo, Michela Ascolani, Manish Kumar, Andreas Hierholzer, Giuseppe Trigiante, Sarah J. Marzi, Philip Avner
Summary: Chd8 is a key regulator of mammalian Xist expression, activating it in embryonic stem cells and preventing spurious Xist expression in differentiating cells. Xist plays a crucial role in X chromosome inactivation by recruiting repressive histone and DNA modifiers, with its regulation tightly coupled to differentiation. Chromatin remodelers like Chd8 have a new role in Xist regulation and contribute to developmentally-regulated gene expression.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Emanuela Viggiano, Luisa Politano
Summary: Anderson-Fabry disease is an X-linked genetic disorder with higher incidence in affected males, but also poses risks for female carriers. The clinical symptoms of the disease are diverse, and studies suggest a correlation between skewed X chromosome inactivation and symptoms in carriers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biology
Aline Muyle, Doris Bachtrog, Gabriel A. B. Marais, James M. A. Turner
Summary: This article discusses how epigenetics influence sex chromosome evolution in animals and plants, focusing on the degeneration of Y chromosome and the inactivation of X chromosome in populations. It also explores the similarities and possible differences between the two processes.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Article
Developmental Biology
Saya Ichihara, Koji Nagao, Takehisa Sakaguchi, Chikashi Obuse, Takashi Sado
Summary: Stable silencing of the inactive X chromosome (Xi) in female mammals is crucial for the development of embryos and their postnatal health. SmcHD1 plays an important role in this process by facilitating the formation of H3K9me3-enriched blocks on the Xi, which in combination with H3K27me3, leads to robust heterochromatin formation. Deficiency of SmcHD1 results in the loss of H3K9me3, causing aberrant distribution of H3K27me3 on the Xi and derepression of X-inactivated genes.
Article
Endocrinology & Metabolism
Laura C. Lane, Kathleen R. Allinson, Katy Campbell, Ishita Bhatnagar, Lorna Ingoe, Salman Razvi, Tim Cheetham, Heather J. Cordell, Simon H. Pearce, Anna L. Mitchell
CLINICAL ENDOCRINOLOGY
(2019)
Letter
Medicine, General & Internal
Salman Razvi, Robin Peeters, Simon H. S. Pearce
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2019)
Article
Endocrinology & Metabolism
Catherine Napier, Earn H. Gan, Anna L. Mitchell, Lorna C. Gilligan, D. Aled Rees, Carla Moran, Krishna Chatterjee, Bijay Vaidya, R. Andrew James, Yaasir Mamoojee, Simon Ashwell, Wiebke Arlt, Simon H. S. Pearce
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2020)
Article
Endocrinology & Metabolism
Catherine Napier, Kathleen Allinson, Earn H. Gan, Anna L. Mitchell, Lorna C. Gilligan, Angela E. Taylor, Wiebke Arlt, Simon H. S. Pearce
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2020)
Review
Endocrinology & Metabolism
Laura C. Lane, Tim D. Cheetham, Petros Perros, Simon H. S. Pearce
Article
Endocrinology & Metabolism
Claire L. Wood, Michael Cole, Malcolm Donaldson, David B. Dunger, Ruth Wood, Niamh Morrison, John N. S. Matthews, Simon H. S. Pearce, Timothy D. Cheetham
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2020)
Article
Endocrinology & Metabolism
Marissa Penna-Martinez, Gesine Meyer, Anette Boe Wolff, Beate Skinningsrud, Corrado Betterle, Alberto Falorni, William Ollier, Dag Undlien, Eystein Husebye, Simon Pearce, Anna L. Mitchell, Klaus Badenhoop
Summary: This study found that vitamin D deficiency and insufficiency are highly prevalent in AAD patients, with lower levels of 25(OH)D-3 and 1,25(OH)(2)D-3 in Norwegian and German AAD patients. The vitamin D status of MD may be influenced by genetic factors, with individual vitamin D requirements throughout the year.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2021)
Review
Medicine, General & Internal
Eystein S. Husebye, Simon H. Pearce, Nils P. Krone, Olle Kaempe
Summary: Adrenal insufficiency can be caused by various factors such as primary adrenal disorder, adrenocorticotropic hormone deficiency, or suppression of adrenocorticotropic hormone by certain medications. Clinical features include unintentional weight loss, anorexia, hypotension, fatigue, muscle and abdominal pain, and hyponatremia. Diagnosis is often delayed due to non-specific symptoms, and patient education on managing the condition is crucial to prevent adrenal crisis.
Article
Endocrinology & Metabolism
Earn H. Gan, Carol Jagger, Mohammad E. Yadegarfar, Rachel Duncan, Simon H. Pearce
Summary: In 85-year-old individuals, declining serum TSH is associated with reductions in free thyroid hormones over time and is a biomarker for cognitive impairment in later life.
Editorial Material
Endocrinology & Metabolism
Tomasz Bednarczuk, Simon H. Pearce
LANCET DIABETES & ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Sophie Howarth, Georgina Sneddon, Kathleen R. Allinson, Salman Razvi, Anna L. Mitchell, Simon H. S. Pearce
Summary: Autoimmune Addison's disease (AAD) is caused by a combination of various genetic susceptibility polymorphisms and environmental factors. A genome-wide association study (GWAS) conducted with Scandinavian Addison's registries identified four novel loci in the LPP, SH2B3, SIGLEC5, and UBASH3A genes that are associated with AAD. A subsequent case-control association study with a UK cohort of 420 AAD patients confirmed significant association of the LPP and UBASH3A genes, and nominal association of the SH2B3 gene with AAD. Further research with larger patient cohorts is needed to confirm the association of SH2B3 and SIGLEC5/SPACA6 alleles.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Letter
Endocrinology & Metabolism
Bruna Barbar, Campbell Mathieson, Chris Boot, Richard Quinton, Andy James, Petros Perros, Simon Pearce, Catherine Napier, Earn Gan, Anna Mitchell, Yaasir H. Mamoojee
CLINICAL ENDOCRINOLOGY
(2023)
Article
Ophthalmology
Petros Perros, Milos Zarkovi, Simon H. Pearce, Salman Razvi, Hema Kolli, A. Jane Dickinson
Summary: The purpose of this study was to determine the inter-observer variability of the Clinical Activity Score (CAS) in patients with thyroid eye disease (TED). The study showed that there is unreliable inter-observer variability in both the total CAS and its individual components. This highlights the need for improving the performance of the CAS or exploring other methods to assess disease activity.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Endocrinology & Metabolism
Lydia Grixti, Laura C. Lane, Simon H. Pearce
Summary: Graves' disease is the most common cause of hyperthyroidism, with a strong familial aggregation and a higher prevalence in women. Genetic factors contribute to 60-80% of the risk of developing Graves' disease. Variants in genes such as HLA, CTLA4, and PTPN22 have been found to play a significant role in disease susceptibility. Additionally, there may be correlations between genetic variants and clinical phenotypes. Over 80 susceptibility loci have been identified so far, and larger studies are needed to investigate the influence of these genetic variants on different phenotypes and treatment outcomes.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2023)
Meeting Abstract
Endocrinology & Metabolism
Claire Wood, Michael Cole, Malcolm Donaldson, David Dunger, John Matthews, Simon Pearce, Tim Cheetham
HORMONE RESEARCH IN PAEDIATRICS
(2019)