Article
Endocrinology & Metabolism
Patrick Hanna, Bruno Francou, Brigitte Delemer, Harald Jueppner, Agnes Linglart
Summary: The study characterized a previously unreported AD-PHP1B family with loss of methylation at GNAS A/B:TSS-DMR, but without evidence for a STX16 deletion on the maternal allele. The research identified distinct methylation changes at the novel GNAS-AS2:TSS-DMR, which may help further characterize different PHP1B/iPPSD3 variants and guide the search for underlying genetic defects.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Patrick Hanna, Bruno Francou, Brigitte Delemer, Harald Juppner, Agnes Linglart
Summary: Pseudohypoparathyroidism type 1B (PHP1B) is characterized by proximal renal tubular resistance to parathyroid hormone (PTH), leading to hypocalcemia. This study aimed to characterize a previously unreported case of autosomal dominant PHP1B with loss of methylation at GNAS A/B:TSS-DMR.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Review
Endocrinology & Metabolism
Wan Yang, Yiyi Zuo, Nuo Zhang, Kangning Wang, Runze Zhang, Ziyi Chen, Qing He
Summary: In this article, the GNAS locus, its associated diseases, signaling pathways, and mouse models are comprehensively explored.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Yamato Keidai, Yorihiro Iwasaki, Kanako Iwasaki, Sachiko Honjo, Murat Bastepe, Akihiro Hamasaki
Summary: Through comprehensive molecular genetic analyses of a pair of monozygotic twins, we found that sporadic pseudohypoparathyroidism type 1B may be caused by methylation defects in the GNAS gene region. Methylation defects in other imprinted genome loci were not found. We ruled out all known genetic causes associated with familial PHP1B and suggested that the causative event may have occurred as an imprinting error prior to the formation of monozygotic twins.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Pauline Romanet, Justine Galluso, Peter Kamenicky, Mirella Hage, Marily Theodoropoulou, Catherine Roche, Thomas Graillon, Heather C. Etchevers, Daniel De Murat, Gregory Mougel, Dominique Figarella-Branger, Henry Dufour, Thomas Cuny, Guillaume Assie, Anne Barlier
Summary: This study found that 40% of somatotroph tumors have GNAS mutations, affecting tumor growth and phenotype. Changes in imprinting may impact GNAS expression levels and tumorigenesis, especially in gsp-negative tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Laura Pignata, Francesco Cecere, Fabio Acquaviva, Emilia D'Angelo, Daniela Cioffi, Valeria Pellino, Orazio Palumbo, Pietro Palumbo, Massimo Carella, Angela Sparago, Daniele De Brasi, Flavia Cerrato, Andrea Riccio
Summary: Imprinting disorders are congenital diseases affecting various aspects of health caused by dysregulation of genomic imprinting. This study reports the co-occurrence of Beckwith-Wiedemann spectrum (BWSp) and Pseudo-hypoparathyroidism type 1B (PHP1B) in a patient without multilocus imprinting disturbances (MLID). Molecular analysis revealed distinct mechanisms for BWSp and PHP1B in this patient. Understanding the molecular mechanisms underlying the co-occurrence of two imprinting disorders can improve genetic counseling and recurrence risk estimation for these rare cases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Endocrinology & Metabolism
Siqi Jiang, Yi Yang, An Song, Yue Jiang, Yan Jiang, Mei Li, Weibo Xia, Min Nie, Ou Wang, Xiaoping Xing
Summary: This study summarized the molecular genetics results and clinical characteristics of PHP1a patients and explored the correlations between them. The results showed that loss-of-function genetic variants were associated with round faces and subcutaneous ossifications.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Yorihiro Iwasaki, Cagri Aksu, Monica Reyes, Birol Ay, Qing He, Murat Bastepe
Summary: Genetic defects of GNAS are responsible for multiple diseases, and abnormal imprinting at the GNAS A/B region causes pseudohypoparathyroidism type 1B. Utilizing a human embryonic stem cell model, we demonstrated the importance of the NESP-ICR in methylation and transcriptional silencing of the GNAS A/B region, and identified the STX16-ICR as a enhancer for NESP55 transcription. These findings advance our understanding of the pathogenesis of pseudohypoparathyroidism type 1B.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Jennifer Danzig, Dong Li, Suzanne Jan de Beur, Michael A. Levine
Summary: Patients with pseudohypoparathyroidism type 1b (PHP1b) exhibit disordered imprinting or paternal uniparental disomy. Researchers identified diverse defective methylation patterns and novel or known mutations in 9 out of 12 PHP1b families.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Tatsuki Urakawa, Shinichiro Sano, Sayaka Kawashima, Akie Nakamura, Hirohito Shima, Motoki Ohta, Yuki Yamada, Ai Nishida, Hiromune Narusawa, Yoshiaki Ohtsu, Keiko Matsubara, Sumito Dateki, Yoshihiro Maruo, Maki Fukami, Tsutomu Ogata, Masayo Kagami
Summary: This study aimed to investigate the clinical characteristics of pseudohypoparathyroidism type 1B (PHP1B). Patients were classified into different groups based on the methylation defects and etiologies, and their clinical findings were compared. The study found that patients in Group 2 (G2) had a younger age at diagnosis and higher levels of intact parathyroid hormone. They were more likely to experience seizures or loss of consciousness. Additionally, some patients also had neurodevelopmental disorders.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Tanguy Demaret, Rene Wintjens, Gwenaelle Sana, Joachim Docquir, Frederic Bertin, Christophe Ide, Olivier Monestier, Deniz Karadurmus, Valerie Benoit, Isabelle Maystadt
Summary: This study reports a rare case of PTH resistance in a child with biallelic mutations in the PTH1R gene, expanding the phenotypic spectrum of iPPSD1. The patient exhibited symptoms such as hypocalcemia, hyperphosphatemia, and abnormalities in tooth development and neurodevelopment.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Quixia Cui, Cagri Aksu, Birol Ay, Claire E. Remillard, Antonius Plagge, Mina Gardezi, Margaret Dunlap, Louis C. Gerstenfeld, Qing He, Murat Bastepe
Summary: Studies have shown that XLαs is predominantly paternally expressed, but there are varying degrees of biallelic expression in bone marrow stromal cells and bone cells. Aberrant differentiation due to constitutively activating GNAS mutations affecting both Gsα and XLαs may be the pathological mechanism underlying fibrous dysplasia of bone.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Sanaa Choufani, Jung Min Ko, Youliang Lou, Cheryl Shuman, Leona Fishman, Rosanna Weksberg
Summary: This case report presents a male patient with both BWS and PHP1b, caused by loss of methylation at chromosome 11p15.5 and paternal isodisomy of chromosome 20. This is the first case demonstrating etiologic heterogeneity for multiple imprinting disorders in a single individual.
Article
Genetics & Heredity
Yu Liu, Ying Yang, Liming Chu, Shuai Ren, Ying Li, Aimin Gao, Jing Wen, Wanling Deng, Yan Lu, Lingyin Kong, Bo Liang, Xiaoshan Shao
Summary: This article presents a case of a Chinese boy with a rare interstitial deletion in the long arm of chromosome 20, containing the GNAS locus. The patient's clinical symptoms and treatment outcomes are described, providing valuable information for the diagnosis and treatment of similar cases.
FRONTIERS IN GENETICS
(2022)
Article
Chemistry, Analytical
Shiting Zhang, Zhiqiang Liu, Siyu Jin, Yufei Bai, Xingjia Feng, Guoqi Fu
Summary: Epitope imprinting on sacrificial asymmetric template-modified Janus nanocores is a promising approach for fabricating oriented surface epitope-imprinted open-mouthed polymer nanocapsules. The resulting OM-MIP NCs show fast fluorescence response and excellent target protein detection performance.
Article
Genetics & Heredity
Carlos R. Ferreira, Mary E. Hackbarth, Shira G. Ziegler, Kristen S. Pan, Mary S. Roberts, Douglas R. Rosing, Margaret S. Whelpley, Joy C. Bryant, Ellen F. Macnamara, Sisi Wang, Kerstin Mueller, Iris R. Hartley, Emily Y. Chew, Timothy E. Corden, Christina M. Jacobsen, Ingrid A. Holm, Frank Rutsch, Esra Dikoglu, Marcus Y. Chen, M. Zulf Mughal, Michael A. Levine, Rachel I. Gafni, William A. Gahl
Summary: Generalized arterial calcification of infancy (GACI) is usually caused by deficiency of ENPP1, and the natural history of GACI survivors has not been established. Out of 20 subjects, 16 presented with arterial calcifications, but only 5 had residual involvement at the time of evaluation.
GENETICS IN MEDICINE
(2021)
Review
Hematology
Kamyar Kalantar-Zadeh, Tomas Ganz, Henry Trumbo, Melvin H. Seid, Lawrence T. Goodnough, Michael A. Levine
Summary: Phosphorus plays a crucial role in cellular and extracellular metabolism, and maintaining phosphorus homeostasis is vital. Intravenous iron formulations can lead to renal phosphate excretion and hypophosphatemia by increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into acute symptomatic and chronic hypophosphatemia, considering pre-existing conditions, medications, and intravenous iron's role. This review focuses on phosphorus homeostasis and hypophosphatemia, emphasizing the effects of iron deficiency and intravenous iron replacement.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Endocrinology & Metabolism
Carlos R. Ferreira, Dillon Kavanagh, Ralf Oheim, Kristin Zimmerman, Julian Stuerznickel, Xiaofeng Li, Paul Stabach, R. Luke Rettig, Logan Calderone, Colin MacKichan, Aaron Wang, Hunter A. Hutchinson, Tracy Nelson, Steven M. Tommasini, Simon von Kroge, Imke A. K. Fiedler, Ethan R. Lester, Gilbert W. Moeckel, Bjoern Busse, Thorsten Schinke, Thomas O. Carpenter, Michael A. Levine, Mark C. Horowitz, Demetrios T. Braddock
Summary: Mutations in ENPP1 can lead to early-onset osteoporosis and autosomal recessive hypophosphatemic rickets. Traditional therapy improved rickets but did not address low bone mineral density, highlighting the potential efficacy of ENPP1 enzyme replacement therapy.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Genetics & Heredity
Colin P. Hawkes, Michael A. Levine
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2021)
Article
Endocrinology & Metabolism
Nina Lenherr-Taube, Michelle Furman, Esther Assor, Yesmino Elia, Carol Collins, Kenneth Thummel, Michael A. Levine, Etienne Sochett
Summary: Idiopathic infantile hypercalcemia is a rare disorder with variable clinical features and the response to dietary calcium and vitamin D restriction in mild cases is not able to consistently normalize elevated 1,25(OH)2D concentrations or prevent worsening of renal calcification. Therapeutic options should focus on the defect in vitamin D metabolism.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Shira London, Michael A. Levine, Dong Li, Ronen Spiegel, Asaf Lebel, Rephael Halevy, Yardena Tenenbaum-Rakover
Summary: This study describes a child who presented with hypocalcemic seizure at the age of 2.3 years. Whole exome sequencing identified a known homozygous missense mutation in the KCNJ1 gene associated with type 2 BS. The findings expand the clinical spectrum of KCNJ1 mutations and highlight the role of WES in cases of hypocalcemia with suspected genetic causes.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Colin P. Hawkes, Jamal M. Al Jubeh, Dong Li, Susan E. Tucker, Tara Rajiyah, Michael A. Levine
Summary: Parathyroid hormone (PTH) gene mutations are rare causes of hypoparathyroidism, which can lead to decreased or elevated levels of PTH. This study describes two novel mutations of the PTH gene, expanding our understanding of the molecular basis for familial isolated hypoparathyroidism (FIH).
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Endocrinology & Metabolism
Ashley J. Stoffers, David R. Weber, Michael A. Levine
Summary: This review provides the most up-to-date understanding of the pathogenesis, prevention, and treatment of vitamin D deficient rickets in children. Risk factors for developing this disorder include inadequate sunlight exposure, exclusive breast feeding without vitamin D supplementation, and inadequate intake of vitamin D, calcium, or phosphorus. It is critical to have a thorough understanding of the individual's vitamin D levels, which are influenced by both environmental and genetic factors, for the evaluation and treatment of children with rickets. Further research is needed to determine the ideal vitamin D status across diverse populations and the impact of vitamin D status on overall health.
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
(2022)
Article
Genetics & Heredity
Douglas Ralph, Michael A. Levine, Gabriele Richard, Michelle M. Morrow, Elizabeth K. Flynn, Jouni Uitto, Qiaoli Li
Summary: This article provides a comprehensive review of all the pathogenic variants, likely pathogenic variants, and variants of unknown significance in the ENPP1 gene associated with various genetic disorders. Missense variants are the most common. While there is no apparent genotype-phenotype correlation, specific variants are associated with Cole disease.
Article
Genetics & Heredity
Douglas Ralph, Yvonne Nitschke, Michael A. Levine, Matthew Caffet, Tamara Wurst, Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Sharon F. Terry, Frank Rutsch, Jouni Uitto, Qiaoli Li
Summary: This study reveals that variants in the ENPP1 gene can cause both GACI and classic PXE, increasing the clinical and genetic diversity of hereditary ectopic calcification disorders. Additionally, the correlation between plasma PPi levels and the severity of vascular calcification is found to be limited in this study.
Review
Endocrinology & Metabolism
Janice L. Pasieka, Kelly Wentworth, Caitlin T. Yeo, Serge Cremers, David Dempster, Seiji Fukumoto, Ravinder Goswami, Pascal Houillier, Michael A. Levine, Jesse D. Pasternak, Nancy D. Perrier, Antonio Sitges-Serra, Dolores M. Shoback
Summary: This article utilized a systematic review to investigate the etiologies and pathogenesis of hypoparathyroidism, with a particular focus on new knowledge about parathyroid gland viability and intraoperative parathyroid hormone monitoring. Non-surgical factors, especially genetic factors, play a significant role in hypoparathyroidism. Due to the widespread impact of PTH deficiency on multiple organ systems, the article provides a detailed review of skeletal, renal, neuromuscular, and ocular complications. The burden of illness on patients and their caregivers leads to reduced quality of life and increased social costs for this chronic endocrinopathy.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Review
Endocrinology & Metabolism
Allen W. Root, Michael A. Levine
Summary: The past 50 years of research in pediatric bone and mineral metabolism have led to significant progress in understanding and characterizing disorders that affect the developing skeleton. Key findings include the identification of important proteins and receptors involved in calcium and phosphate metabolism, as well as the genetic causes for various bone and mineral disorders. These discoveries will likely lead to the development of innovative treatments in the next decade that will improve the lives of children with these disorders.
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Amnon Zung, Galia Barash, Ehud Banne, Michael A. Levine
Summary: We report a novel heterozygous mutation in the CASR gene that causes autosomal dominant hypocalcemia type 1. The mutation increases the sensitivity of the CASR to extracellular calcium. Clinical features included seizures, reduced renal calcium reabsorption, and early lens opacity. Based on the comprehensive clinical data, we propose age-specific upper limit of serum calcium levels to balance the risk of seizures and hypercalciuria.
HORMONE RESEARCH IN PAEDIATRICS
(2023)
Article
Endocrinology & Metabolism
Nelson B. Watts, John P. Bilezikian, Henry G. Bone, Bart L. Clarke, Douglas Denham, Michael A. Levine, Michael Mannstadt, Munro Peacock, Jeffrey G. Rothman, Tamara J. Vokes, Mark L. Warren, Shaoming Yin, Nicole Sherry, Dolores M. Shoback
Summary: This study evaluated the long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment for chronic hypoparathyroidism. The results showed sustained improvements in biochemical parameters, a reduction in the percentage of patients with hypercalciuria, stable renal function, and decreased supplement requirements over 6 years of treatment with rhPTH(1-84). rhPTH(1-84) was well tolerated, and no new safety signals were identified.
JOURNAL OF THE ENDOCRINE SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Oelisoa M. Andriankaja, Reuben Adatorwovor, Alpdogan Kantarci, Hatice Hasturk, Luciana Shaddox, Michael A. Levine
Summary: This study assessed the association between serum or gingival crevicular fluid endothelial and inflammatory mediators and chronic periodontal disease among Hispanic adults with type 2 diabetes. The findings showed that oral and systemic endothelial and inflammatory mediators are related to periodontal clinical parameters.