Article
Obstetrics & Gynecology
Leigh A. M. Demain, Eline Boetje, Jonathan J. Edgerley, Emma Miles, Cheryl T. Fitzgerald, Gail Busby, Glenda M. Beaman, James O'Sullivan, Raymond T. O'Keefe, William G. Newman
Summary: A 21-year-old woman with primary amenorrhoea was found to have a nonsense variant and whole gene deletion in STAG3, which are associated with primary ovarian failure type 8 and are a rare cause of POI.
REPRODUCTIVE BIOMEDICINE ONLINE
(2021)
Article
Genetics & Heredity
Kunal P. Verma, Bryony Thompson, James Wolfe, Sarah Price, Frida Djukiadmodjo, Alison Trainer
Summary: Premature or primary ovarian insufficiency (POI) affects approximately 1% of women and can be caused by a variety of genetic factors. Research has shown an association between GDF9 gene and POI, suggesting routine evaluation for GDF9 variants in patients undergoing genomic investigation for POI.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2021)
Review
Genetics & Heredity
Simona Mellone, Marco Zavattaro, Denise Vurchio, Sara Ronzani, Marina Caputo, Ilaria Leone, Flavia Prodam, Mara Giordano
Summary: Primary ovarian insufficiency (POI) is a heterogeneous disorder characterized by hypergonadotropic hypogonadism, often leading to female infertility. While some cases have a genetic basis, most remain unresolved. A 19-year-old female with non-syndromic POI was found to have a novel homozygous mutation in the STAG3 gene, highlighting its role in meiosis.
Article
Endocrinology & Metabolism
Svetlana A. Yatsenko, Fatih Gurbuz, Ali Kemal Topaloglu, Andrea J. Berman, Pierre-Marie Martin, Marta Rodrigue-Escriba, Yingying Qin, Aleksandar Rajkovic
Summary: This study identified pathogenic variants in the ZSWIM7 gene associated with primary ovarian insufficiency (POI), highlighting the importance of this gene in DNA damage response during meiosis and its role in ovarian development and function. Characterization of patients with defects in DNA repair genes has important diagnostic and prognostic consequences for clinical management and reproductive decisions.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Monica M. Franca, Yazmine B. Condezo, Maeva Elzaiat, Natalia Felipe-Medina, Fernando Sanchez-Saez, Sergio Munoz, Raquel Sainz-Urruela, M. Rosario Martin-Hervas, Rodrigo Garcia-Valiente, Manuel A. Sanchez-Martin, Aurora Astudillo, Juan Mendez, Elena Llano, Reiner A. Veitia, Berenice B. Mendonca, Alberto M. Pendas
Summary: A homozygous RAD51B variant was identified in sisters with POI, leading to DNA repair defects and reduced crossovers. This variant also affected RAD51B interactions and replication fork progression, indicating a role in somatic genome stability maintenance.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Genetics & Heredity
Arvand Akbari, Seyedeh Zoha Tabatabaei, Najmeh Salehi, Kimiya Padidar, Navid Almadani, Mohammad Ali Sadighi Gilani, Mehri Mashayekhi, Elahe Motevaseli, Mehdi Totonchi
Summary: A novel in-frame deletion and a novel missense variant in STAG3 were found among a patient with primary ovarian failure and her two brothers with non-obstructive azoospermia, potentially disrupting the protein's meiotic functions.
Article
Genetics & Heredity
Yurong Wang, Ling Liu, Chen Tan, Guiquan Meng, Lanlan Meng, Hongchuan Nie, Juan Du, Guang-Xiu Lu, Ge Lin, Wen-Bin He, Yue-Qiu Tan
Summary: This study identified three novel MEIOB loss-of-function variants in three Han Chinese families with premature ovarian insufficiency (POI) or non-obstructive azoospermia (NOA) using whole-exome sequencing. In vitro functional analyses confirmed the pathogenicity of these variants. These findings extend the mutation spectrum of the MEIOB gene and have important implications for genetic counseling in affected families.
FRONTIERS IN GENETICS
(2022)
Article
Endocrinology & Metabolism
Elinor C. Vogt, Lars Breivik, Ellen C. Royrvik, Marianne Grytaas, Eystein S. Husebye, Marianne Oksnes
Summary: This study found that 10.2% of women with autoimmune Addison's disease (AAD) have Primary Ovarian Insufficiency (POI), with approximately one-third developing POI before the age of 30. Autoantibodies against side-chain cleavage enzyme (SCC) had a 96% negative predictive value for POI. Additionally, the use of hormone replacement therapy (HRT) was higher in women with AAD compared to the general population.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Review
Endocrinology & Metabolism
Xiaojun Kuang, Yongzhe Tang, Hong Xu, Min Ji, Dongmei Lai
Summary: This review assesses the effectiveness of various therapies in recovering ovarian function in patients with primary ovarian insufficiency (POI) and explores a comprehensive evaluation method. The results indicate a lack of scientific evidence supporting any therapy in effectively restoring ovarian function in patients with POI.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Engineering, Biomedical
Sichen Zhang, Dashuai Zhu, Xuan Mei, Zhenhua Li, Junlang Li, Mengjie Xie, Halle Jiang Williams Xie, Shaowei Wang, Ke Cheng
Summary: POI is a type of ovarian dysfunction affecting over 1% of women, with HRT being the common treatment to alleviate symptoms but unable to restore ovarian functions. Stem cell therapy is a proposed emerging treatment for POI, which requires further research to establish effective treatment strategies.
BIOACTIVE MATERIALS
(2021)
Article
Cell & Tissue Engineering
Hang-soo Park, Rishi Man Chugh, Jin Seok, Esra Cetin, Hanaa Mohammed, Hiba Siblini, Farzana Liakath Ali, Mohammad Mousaei Ghasroldasht, Hiba Alkelani, Amro Elsharoud, Mara Ulin, Sahar Esfandyari, Ayman Al-Hendy
Summary: This study compared the therapeutic effects of MSCs and equal amounts of MSC-derived exosomes in a POI mouse model. The results showed that although there were some differences, both treatments were able to achieve pregnancy in the POI mouse model.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Genetics & Heredity
Sandrine Caburet, Abdelkader Heddar, Elodie Dardillac, Helene Creux, Marie Lambert, Sebastien Messiaen, Sophie Tourpin, Gabriel Livera, Bernard S. Lopez, Micheline Misrahi
Summary: This study reports a novel phenotype of isolated POI with a BRCA2 variant in a consanguineous Turkish family. Functional studies revealed that BRCA2 is expressed in human fetal ovaries and the patient did not exhibit cancer predisposition or FA traits. The findings extend the phenotype of BRCA2 biallelic alterations to fully isolated POI, impacting the management and genetic counseling of POI patients.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Endocrinology & Metabolism
Cynthia A. Stuenkel, Anne Gompel, Susan R. Davis, JoAnn Pinkerton, Mary Ann Lumsden, Richard J. Santen
Summary: Menstrual cyclicity is important for reproductive health in women, and amenorrhea can indicate disruptions in the reproductive system. Primary ovarian insufficiency is a challenging disorder that requires further research for fertility restoration and hormone replacement therapy.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Qian Zhang, Chengqiu Tao, Shuchang Gao, Shan Li, Bingying Xu, Hanni Ke, Yiyang Wang, Feng Zhang, Yingying Qin, Ling Zhang, Ting Guo
Summary: A splicing site variant in KASH5 is responsible for POI due to defective meiotic homolog pairing and accelerated depletion of oocytes. Our study is the first to report the involvement of disorganized LINC complex in the pathogenesis of POI, potentially suggesting the essential roles of meiotic telomere attachment and dynein-driven proteins for chromosome movement in ovarian function maintenance.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Medicine, Research & Experimental
Sichen Zhang, Dashuai Zhu, Zhenhua Li, Ke Huang, Shiqi Hu, Halle Lutz, Mengjie Xie, Xuan Mei, Junlang Li, Genevieve Neal-Perry, Shaowei Wang, Ke Cheng
Summary: The therapeutic ovarian regenerative patch (ORP) has been found to effectively treat POI and restore fertility in rats by stimulating the proliferation of ovarian somatic cells and inhibiting apoptosis under injury stress. This cell-free, off-the-shelf, and clinically feasible treatment represents a promising approach for POI.
Article
Endocrinology & Metabolism
Sinead M. McGlacken-Byrne, Polona Le Quesne Stabej, Ignacio Del Valle, Louise Ocaka, Andrey Gagunashvili, Berta Crespo, Nadjeda Moreno, Chela James, Chiara Bacchelli, Mehul T. Dattani, Hywel J. Williams, Dan Kelberman, John C. Achermann, Gerard S. Conway
Summary: In this study, a genetic mechanism underlying early-onset POI in two sisters was identified. The disruption of the ZSWIM7 gene was found to be associated with POI in humans and may play an important role in human homologous recombination. This study expands the range of genes associated with POI in women.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Oncology
Reda Stankunaite, Sally L. George, Lewis Gallagher, Sabri Jamal, Ridwan Shaikh, Lina Yuan, Debbie Hughes, Paula Z. Proszek, Paul Carter, Grzegorz Pietka, Timon Heide, Chela James, Haider Tari, Claire Lynn, Neha Jain, Laura Rey Portela, Tony Rogers, Sucheta J. Vaidya, Julia C. Chisholm, Fernando Carceller, Elwira Szychot, Henry Mandeville, Paola Angelini, Angela B. Jesudason, Michael Jackson, Lynley Marshall, Susanne A. Gatz, John Anderson, Andrea Sottoriva, Louis Chesler, Michael Hubank
Summary: This study developed a clinically relevant NGS capture panel and workflow for detecting low frequency genetic variants in cell-free DNA from children with solid tumors. The method showed high sensitivity, specificity, repeatability, and reproducibility. The potential for clinical application was demonstrated in childhood cancer patients, with a close correlation between cfDNA events and treatment response observed.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Genetics & Heredity
Leyla Akin, Karine Rizzoti, Louise C. Gregory, Beatriz Corredor, Polona Le Quesne Stabej, Hywel Williams, Federica Buonocore, Stephane Mouilleron, Valeria Capra, Sinead M. McGlacken-Byrne, Gabriel A. Martos-Moreno, Dimitar N. Azmanov, Mustafa Kendirci, Selim Kurtoglu, Jenifer P. Suntharalingham, Christophe Galichet, Stefano Gustincich, Velibor Tasic, John C. Achermann, Andrea Accogli, Aleksandra Filipovska, Anatoly Tuilpakov, Mohamad Maghnie, Zoran Gucev, Zeynep Burcin Gonen, Luis A. Perez-Jurado, Iain Robinson, Robin Lovell-Badge, Jesus Argente, Mehul T. Dattani
Summary: This study investigates the molecular basis of a novel phenotype involving hypopituitarism associated with primary ovarian insufficiency. The researchers identified pathogenic variants in the RNPC3 gene in patients with the phenotype and explored the role of RNPC3 in gonadal and pituitary development and function.
GENETICS IN MEDICINE
(2022)
Article
Multidisciplinary Sciences
Ifat Geron, Angela Maria Savino, Hila Fishman, Noa Tal, John Brown, Virginia A. Turati, Chela James, Jolanda Sarno, Michal Hameiri-Grossman, Yu Nee Lee, Avigail Rein, Hillary Maniriho, Yehudit Birger, Anna Zemlyansky, Inna Muler, Kara L. Davis, Victoria Marcu-Malina, Nicole Mattson, Oren Parnas, Rabea Wagener, Ute Fischer, Joao T. Barata, Catriona H. M. Jamieson, Markus Muschen, Chun-Wei Chen, Arndt Borkhardt, Ilan Richard Kirsch, Arnon Nagler, Tariq Enver, Shai Izraeli
Summary: This study reveals that activating mutations in Interleukin-7 receptor alpha can initiate preleukemia in primary human hematopoietic progenitors and cooperate with CDKN2A silencing in the progression into acute lymphoblastic leukemia (BCP-ALL).
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Sinead M. McGlacken-Byrne, Ignacio del Valle, Polona Le Quesne Stabej, Laura Bellutti, Luz Garcia-Alonso, Louise A. Ocaka, Miho Ishida, Jenifer P. Suntharalingham, Andrey Gagunashvili, Olumide K. Ogunbiyi, Talisa Mistry, Federica Buonocore, Berta Crespo, Nadjeda Moreno, Paola Niola, Tony Brooks, Caroline E. Brain, Mehul T. Dattani, Daniel Kelberman, Roser Vento-Tormo, Carlos F. Lagos, Gabriel Livera, Gerard S. Conway, John C. Achermann
Summary: Primary ovarian insufficiency (POI) affects 1% of women and is associated with significant medical and psychosocial consequences. Recent research has identified pathogenic variants in the YTHDC2 gene that are linked to early-onset POI, highlighting the importance of this gene in human meiosis regulation.
Article
Multidisciplinary Sciences
Tarjinder Singh, Timothy Poterba, David Curtis, Huda Akil, Mariam Al Eissa, Jack D. Barchas, Nicholas Bass, Tim B. Bigdeli, Gerome Breen, Evelyn J. Bromet, Peter F. Buckley, William E. Bunney, Jonas Bybjerg-Grauholm, William F. Byerley, Sinead B. Chapman, Wei J. Chen, Claire Churchhouse, Nicholas Craddock, Caroline M. Cusick, Lynn DeLisi, Sheila Dodge, Michael A. Escamilla, Saana Eskelinen, Ayman H. Fanous, Stephen Faraone, Alessia Fiorentino, Laurent Francioli, Stacey B. Gabriel, Diane Gage, Sarah A. Gagliano Taliun, Andrea Ganna, Giulio Genovese, David C. Glahn, Jakob Grove, Mei-Hua Hall, Eija Hamalainen, Henrike O. Heyne, Matti Holi, David M. Hougaard, Daniel P. Howrigan, Hailiang Huang, Hai-Gwo Hwu, Rene S. Kahn, Hyun Min Kang, Konrad J. Karczewski, George Kirov, James A. Knowles, Francis S. Lee, Douglas S. Lehrer, Francesco Lescai, Dolores Malaspina, Stephen R. Marder, Steven A. McCarroll, Andrew M. McIntosh, Helena Medeiros, Lili Milani, Christopher P. Morley, Derek W. Morris, Preben Bo Mortensen, Richard M. Myers, Merete Nordentoft, Niamh L. O'Brien, Ana Maria Olivares, Dost Ongur, Willem H. Ouwehand, Duncan S. Palmer, Tiina Paunio, Digby Quested, Mark H. Rapaport, Elliott Rees, Brandi Rollins, F. Kyle Satterstrom, Alan Schatzberg, Edward Scolnick, Laura J. Scott, Sally Sharp, Pamela Sklar, Jordan W. Smoller, Janet L. Sobell, Matthew Solomonson, Eli A. Stahl, Christine R. Stevens, Jaana Suvisaari, Grace Tiao, Stanley J. Watson, Nicholas A. Watts, Douglas H. Blackwood, Anders D. Borglum, Bruce M. Cohen, Aiden P. Corvin, Tonu Esko, Nelson B. Freimer, Stephen J. Glatt, Christina M. Hultman, Andrew McQuillin, Aarno Palotie, Carlos N. Pato, Michele T. Pato, Ann E. Pulver, David St Clair, Ming T. Tsuang, Marquis P. Vawter, James T. Walters, Thomas M. Werge, Roel A. Ophoff, Patrick F. Sullivan, Michael J. Owen, Michael Boehnke, Michael C. O'Donovan, Benjamin M. Neale, Mark J. Daly
Summary: Rare coding variants in certain genes, particularly those related to the function of the nervous system, are found to be significantly associated with schizophrenia. The involvement of specific receptor subunits in the glutamatergic system supports the hypothesis of dysfunction in this system as a mechanism in the development of schizophrenia. The findings suggest that both common and rare genetic risk factors are involved in the pathogenesis of schizophrenia, and more risk genes are yet to be discovered using this approach.
Review
Endocrinology & Metabolism
Avinaash Maharaj, Ruth Kwong, Jack Williams, Christopher Smith, Helen Storr, Ruth Krone, Debora Braslavsky, Maria Clemente, Nanik Ram, Indraneel Banerjee, Semra Cetinkaya, Federica Buonocore, Tulay Guran, John C. Achermann, Louise Metherell, Rathi Prasad
Summary: SPLIS is a syndrome characterized by various endocrine disorders, with glucocorticoid insufficiency and adrenal insufficiency being the most common manifestations. Other endocrine abnormalities include mineralocorticoid deficiency, primary gonadal insufficiency, and mild primary hypothyroidism. There is no clear genotype-phenotype correlation, but certain variants are consistently associated with specific endocrine phenotypes.
ENDOCRINE CONNECTIONS
(2022)
Editorial Material
Genetics & Heredity
Jana Jezkova, Sophie Shaw, Nicola Taverner, Hywel J. Williams
Summary: This article discusses the application of rapid NGS techniques in diagnosing pediatric patients with suspected rare diseases, highlighting the associated challenges and future developments in this field.
Article
Medicine, General & Internal
Joseph Freer, Joanna Orr, Joan K. Morris, Robert Walton, Leo Dunkel, Helen L. Storr, Andrew J. Prendergast
Summary: Short stature at age 3 is associated with lower language development scores from 3 to 11 years of age in UK children, and this association remains significant after adjusting for other factors.
Article
Primary Health Care
H. L. Storr, J. Freer, J. Child, J. H. Davies
BRITISH JOURNAL OF GENERAL PRACTICE
(2023)
Editorial Material
Primary Health Care
Justin H. Davies, Jenny Child, Joseph Freer, Helen L. Storr
BRITISH JOURNAL OF GENERAL PRACTICE
(2023)
Article
Cell Biology
Katrin M. Schuele, Jelena Weckerle, Simone Probst, Alexandra E. Wehmeyer, Lea Zissel, Chiara M. Schroeder, Mehmet Tekman, Gwang-Jin Kim, Inga-Marie Schlaegl, Sagar, Sebastian J. Arnold
Summary: Eomes and Brachyury exhibit distinct transcriptional activities, guiding the specification of specific cell lineages. While their binding sites overlap at the promoters of target genes, they show specificity for distal enhancer regions.
DEVELOPMENTAL CELL
(2023)
Article
Biochemical Research Methods
Mariangela Santorsola, Francesco Lescai
Summary: Deep learning has revolutionised data processing and enabled accurate prediction and classification. Explainable deep learning is emerging as a tool to address issues like transparency and empower AI to provide new insights into biological data.
Article
Pediatrics
Gemma White, Shakira Cosier, Afiya Andrews, Lee Martin, Ruben Willemsen, Martin O. Savage, Helen L. Storr
Summary: This observational study evaluated the sensitivity and specificity of UK and Dutch referral criteria for predicting pathological short stature. The UK criteria showed limited sensitivity and specificity, while the Dutch criteria had higher sensitivity. Considering the child's genetic height potential before referral can prevent unnecessary assessments.
BMJ PAEDIATRICS OPEN
(2022)