Article
Endocrinology & Metabolism
Francesco Carlomagno, Carlotta Pozza, Marta Tenuta, Riccardo Pofi, Luigi Tarani, Franz Sesti, Marianna Minnetti, Daniele Gianfrilli, Andrea M. Isidori
Summary: This study analyzed the testicular microcirculation in Klinefelter syndrome (KS) using contrast-enhanced ultrasonography (CEUS) and found that KS patients have slower testicular blood flow dynamics compared to controls, with reduced venous blood flow independently predicting peripheral release of testosterone (T).
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Guillermo Galdon, Nicholas A. Deebel, Nima Pourhabibi Zarandi, Mark J. Pettenati, Stanley Kogan, Christina Wang, Ronald S. Swerdloff, Anthony Atala, Yanhe Lue, Hooman Sadri-Ardekani
Summary: This study provides the first evidence of the loss of an extra sex chromosome during innate SSC culture, which is crucial for treating Klinefelter syndrome (KS) patients and preserving and propagating SSCs for future sperm production, either in vitro or in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Obstetrics & Gynecology
Lucie Renault, Elsa Labrune, Sandrine Giscard D'Estaing, Beatrice Cuzin, Marion Lapoirie, Mehdi Benchaib, Jacqueline Lornage, Gaelle Soignon, Andre de Souza, Frederique Dijoud, Eloise Fraison, Laurence Pral-Chatillon, Agnes Bordes, Damien Sanlaville, Caroline Schluth-Bolard, Bruno Salle, Rene Ecochard, Herve Lejeune, Ingrid Plotton
Summary: Age appears not to be a factor affecting the success rate of TESE in non-mosaic KS patients. Anti-Mullerian hormone (AMH) has a better predictive value and can guide clinician decision-making and patient information.
HUMAN REPRODUCTION
(2022)
Article
Neurosciences
Ethan T. Whitman, Siyuan Liu, Erin Torres, Allysa Warling, Kathleen Wilson, Ajay Nadig, Cassidy McDermott, Liv S. Clasen, Jonathan D. Blumenthal, Francois M. Lalonde, Stephen J. Gotts, Alex Martin, Armin Raznahan
Summary: Our study identified increased global resting-state functional connectivity in the left dorsolateral prefrontal cortex in XXY syndrome, which was partly linked to regional volumetric changes and severity of psychopathology. This provides biological insights into XXY syndrome as a disorder and a model of genetic risk for psychopathology.
Review
Genetics & Heredity
Rosalia Sa, Luis Ferraz, Alberto Barros, Mario Sousa
Summary: Klinefelter syndrome is a common chromosomal sexual anomaly with symptoms including tall stature, small testicles, small penis, feminine body proportions and hair, obesity, and testicular failure. It can also lead to endocrine, musculoskeletal, cardiovascular, autoimmune disorders, cancer, neurocognitive disabilities, and infertility. The retrieval of spermatozoa from the testicles for assisted reproduction treatments is discussed, and the low risk of passing on the genetic defect to children is mentioned.
Article
Endocrinology & Metabolism
Guillermo Galdon, Nicholas A. Deebel, Nima Pourhabibi Zarandi, Darren Teramoto, YanHe Lue, Christina Wang, Ronald Swerdloff, Mark J. Pettenati, William G. Kearns, Stuart Howards, Stanley Kogan, Anthony Atala, Hooman Sadri-Ardekani
Summary: This study successfully isolated and long-term cultured testicular cells from KS patients, confirming the presence of spermatogonial cell population and stem cell population. These findings inform the development of therapeutic fertility options for KS patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Carlotta Pozza, Franz Sesti, Marta Tenuta, Matteo Spaziani, Chiara Tarantino, Francesco Carlomagno, Marianna Minnetti, Riccardo Pofi, Roberto Paparella, Andrea Lenzi, Antonio Radicioni, Andrea M. Isidori, Luigi Tarani, Daniele Gianfrilli
Summary: This study describes the natural history of testicular dysfunction in patients with Klinefelter syndrome through the integration of clinical, hormonal, and quantitative ultrasound data. The results show that testicular development progresses until Tanner stage 4, with subsequent regression. Hormonal detection of Sertoli and germ cell impairment is not observed until Tanner stages 3-4. The findings highlight the importance of quantitative testicular ultrasound in infancy, childhood, and during pubertal development and transition age for optimal care of Klinefelter syndrome patients.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Lara C. Foland-Ross, Elnaz Ghasemi, Vanessa Lozano Wun, Tandy Aye, Karen Kowal, Judith Ross, Allan L. Reiss
Summary: Executive dysfunction is a common cognitive phenotype in adolescents with Klinefelter syndrome (KS), and it is associated with testicular failure. This study found that boys with KS have lower executive function and reduced brain activation in regions related to executive function. The severity of pubertal developmental delay, indicated by lower testosterone and testes volume, was associated with the magnitude of activation differences in boys with KS.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Obstetrics & Gynecology
Emma B. Johannsen, Anne Skakkebaek, Joanna M. Kalucka, Jens Fedder, Claus H. Gravholt, Jesper Just
Summary: This study investigates the gene expression pattern at the single-cell level in the testes of individuals with Klinefelter syndrome (KS) and its association with microvascular dysfunction. The findings suggest excessive endothelial cell activation, disorganized vessel formation, and compromised vessel integrity in individuals with KS.
HUMAN REPRODUCTION
(2023)
Article
Genetics & Heredity
Carole Samango-Sprouse, Michaela Reiko Brooks, Patricia Lasutchinkow, Teresa Sadeghin, Sherida Powell, Mary Pat Hamzik, Sophia Song, Andrea L. Gropman
Summary: The study demonstrates that early hormonal treatment in boys with 47,XXY can help improve their expressive and receptive language capabilities during early childhood, which is crucial for fostering reading skills and academic success later in life.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Line Dahl Jeppesen, Tina Duelund Hjortshoj, Johnny Hindkjaer, Lotte Hatt, Olav Bjorn Petersen, Ripudaman Singh, Palle Schelde, Lotte Andreasen, Rikke Christensen, Dorte L. Lildballe, Ida Vogel
Summary: The article introduces a cell-based noninvasive prenatal DNA testing method applied to twin pregnancies to assist couples in prenatal testing decision-making.
FRONTIERS IN GENETICS
(2022)
Review
Genetics & Heredity
Tinka Hovnik, Eva Zitnik, Magdalena Avbelj Stefanija, Sara Bertok, Katarina Sedej, Vesna Bancic Silva, Tadej Battelino, Urh Groselj
Summary: Klinefelter syndrome is a commonly reported sex chromosome abnormality, which is heavily underdiagnosed due to its substantial clinical variability. This study presents a case of a male phenotype with a rare variant mosaic 47,XXY/46,XX karyotype and summarizes the clinical presentations of reported male patients with 47,XXY/46,XX mosaicism.
Article
Genetics & Heredity
Luisa Ronzoni, Maria Francesca Bedeschi, Gaia Silibello, Veronica Accurti, Marina Di Segni, Valeria Nicotra, Paola Vizziello, Faustina Lalatta
Summary: This study highlights the unconfirmed increased risk of 47,XXY in cfDNA tests, suggesting the need for discussion on invasive testing to exclude more severe chromosomal variations.
PRENATAL DIAGNOSIS
(2021)
Article
Genetics & Heredity
Carole Samango-Sprouse, Michaela Reiko Brooks, Debra Counts, Mary Pat Hamzik, Sophia Song, Sherida Powell, Teresa Sadeghin, Andrea L. Gropman
Summary: This study aimed to investigate the effects of different hormone replacement therapies on neuromotor function in males with 47,XXY. The results showed that the early hormonal treatment group performed better than the untreated group in infancy, and males who received early treatment had improved scores in multiple motor domains during school-age years. The study suggests that hormone replacement therapy may play a long-term promoting role in the neuromotor outcomes of males with 47,XXY.
GENETICS IN MEDICINE
(2022)
Review
Medicine, General & Internal
Jubara Alallah, Sohaib Habhab, Farzeen Mohtisham, Aiman Shawli, Mustafa Daghistani
Summary: This article reports the first case of a Saudi newborn with both Down syndrome and Klinefelter syndrome (double aneuploidy). The patient exhibited clinical features of Down syndrome, along with hypothyroidism and congenital heart disease.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2022)
Review
Obstetrics & Gynecology
Brendan J. Houston, Antoni Riera-Escamilla, Margot J. Wyrwoll, Albert Salas-Huetos, Miguel J. Xavier, Liina Nagirnaja, Corinna Friedrich, Don F. Conrad, Kenneth Aston, Csilla Krausz, Frank Tuttelmann, Moira K. O'Bryan, Joris A. Veltman, Manon S. Oud
Summary: Research has shown a significant genetic component in male infertility, particularly monogenic causes. The field had been slow in adopting next-generation sequencing technologies and lacked clear statements on validated causes of human male infertility. Through clinical validity assessment, 120 genes were identified to be moderately, strongly or definitively linked to 104 infertility phenotypes.
HUMAN REPRODUCTION UPDATE
(2022)
Article
Endocrinology & Metabolism
Brendan J. Houston, Anne E. O'Connor, Degang Wang, Georgia Goodchild, D. Jo Merriner, Haitong Luan, Don F. Conrad, Liina Nagirnaja, Kenneth Aston, Sabine Kliesch, Margot J. Wyrwoll, Corinna Friedrich, Frank Tuettelmann, Craig Harrison, Moira K. O'Bryan, Kelly Walton
Summary: This study reveals the impact of INHBB gene variants on testis composition in males, particularly those that limit activin B production. Although the variants result in significantly larger testes, they do not affect fertility.
Article
Obstetrics & Gynecology
M. J. Wyrwoll, E. S. van Walree, G. Hamer, N. Rotte, M. M. Motazacker, H. Meijers-Heijboer, M. Alders, A. Meissner, E. Kaminsky, M. Woeste, C. Krallmann, S. Kliesch, T. J. Hunt, A. T. Clark, S. Silber, B. Stallmeyer, C. Friedrich, A. M. M. van Pelt, I. B. Mathijssen, F. Tuettelmann
Summary: The study identified bi-allelic variants in MSH4 and MSH5 as causes of male infertility, expanding the understanding of genetic factors contributing to azoospermia.
HUMAN REPRODUCTION
(2022)
Article
Obstetrics & Gynecology
Margot J. Wyrwoll, Frank Tuettelmann
Summary: In about half of infertile couples, the male partner can be diagnosed with a specific condition. Genetic analysis can help establish a causal diagnosis, provide individual counseling and treatment for the couple, and guide treatment decisions. Common genetic causes of male infertility include chromosomal abnormalities, Y chromosome deletions, and gene mutations. Recent studies have identified several genes associated with sperm abnormalities. Detecting the underlying genetic cause of male infertility helps estimate the success rate of assisted reproductive treatments and the risk of recurrence in offspring.
Article
Genetics & Heredity
Antoni Riera-Escamilla, Matthias Vockel, Liina Nagirnaja, Miguel J. Xavier, Albert Carbonell, Daniel Moreno-Mendoza, Marc Pybus, Ginevra Farnetani, Viktoria Rosta, Francesca Cioppi, Corinna Friedrich, Manon S. Oud, Godfried W. van der Heijden, Armin Soave, Thorsten Diemer, Elisabet Ars, Josvany Sanchez-Curbelo, Sabine Kliesch, Moira K. O'Bryan, Eduard Ruiz-Castane, Fernando Azorin, Joris A. Veltman, Kenneth Aston, Donald F. Conrad, Frank Tuettelmann, Csilla Krausz
Summary: This study provides a significant contribution to the understanding of X chromosome-linked genetic causes of azoospermia/cryptozoospermia. It identifies 21 genes strongly associated with azoospermia/cryptozoospermia and 34 genes moderately associated, including one prioritized gene, RBBP7, which was found mutated in ten men and supported by functional studies in Drosophila.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Endocrinology & Metabolism
Giulia Brigante, Clara Lazzaretti, Elia Paradiso, Federico Nuzzo, Martina Sitti, Frank Tuttelmann, Gabriele Moretti, Roberto Silvestri, Federica Gemignani, Asta Forsti, Kari Hemminki, Rossella Elisei, Cristina Romei, Eric Adriano Zizzi, Marco Agostino Deriu, Manuela Simoni, Stefano Landi, Livio Casarini
Summary: This study investigates the genetic predisposition to differentiated thyroid carcinoma (DTC) by analyzing single nucleotide polymorphisms (SNPs) using polygenic risk score (PRS), Bayesian statistics, and machine learning (ML) classifier. The findings reveal that a selection of 15 DTC-associated SNPs can accurately predict the case or control status based on individual genetic background.
EUROPEAN THYROID JOURNAL
(2022)
Article
Genetics & Heredity
Margot J. Wyrwoll, Channah M. Gaasbeek, Ieva Golubickaite, Rytis Stakaitis, Manon S. Oud, Liina Nagirnaja, Camille Dion, Emad B. Sindi, Harry G. Leitch, Channa N. Jayasena, Anu Sironen, Ann-Kristin Dicke, Nadja Rotte, Birgit Stallmeyer, Sabine Kliesch, Carlos H. P. Grangeiro, Thais S. F. Araujo, Paul Lasko, Kathleen D'Hauwers, Roos M. Smits, Liliana Ramos, Miguel J. Xavier, Don F. Conrad, Kristian Almstrup, Joris A. Veltman, Frank Tuettelmann, Godfried W. van der Heijden
Summary: FKBP6 variants are associated with male infertility, leading to impaired testicular development and sperm production. Patients with loss-of-function variants in FKBP6 have very few or no sperm in their ejaculate, making them ineligible for assisted reproductive techniques. FKBP6 plays an important role in piRNA biogenesis in humans.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biology
Miriam Cervan-Martin, Frank Tuettelmann, Alexandra M. Lopes, Lara Bossini-Castillo, Rocio Rivera-Egea, Nicolas Garrido, Saturnino Lujan, Gema Romeu, Samuel Santos-Ribeiro, Jose A. Castilla, M. Carmen Gonzalvo, Ana Clavero, Vicente Maldonado, F. Javier Vicente, Sara Gonzalez-Munoz, Andrea Guzman-Jimenez, Miguel Burgos, Rafael Jimenez, Alberto Pacheco, Cristina Gonzalez, Susana Gomez, David Amoros, Jesus Aguilar, Fernando Quintana, Carlos Calhaz-Jorge, Ana Aguiar, Joaquim Nunes, Sandra Sousa, Isabel Pereira, Maria Graca Pinto, Sonia Correia, Josvany Sanchez-Curbelo, Olga Lopez-Rodrigo, Javier Martin, Iris Pereira-Caetano, Patricia I. Marques, Filipa Carvalho, Alberto Barros, Joerg Gromoll, Lluis Bassas, Susana Seixas, Joao Goncalves, Sara Larriba, Sabine Kliesch, Rogelio J. Palomino-Morales, F. David Carmona
Summary: This study identified two genomic regions associated with the most severe phenotype of spermatogenic failure through genome-wide association analysis. The findings suggest that unexplained spermatogenic failure may be influenced by common genetic variations in the genome and have an immune-mediated component.
COMMUNICATIONS BIOLOGY
(2022)
Article
Obstetrics & Gynecology
Kim Joana Westerich, Solveig Reinecke, Jana Emich, Margot Julia Wyrwoll, Birgit Stallmeyer, Matthias Meyer, Manon S. Oud, Daniela Fietz, Adrian Pilatz, Sabine Kliesch, Michal Reichman-Fried, Katsiaryna Tarbashevich, Tamara Limon, Martin Stehling, Corinna Friedrich, Frank Tuettelmann, Erez Raz
Summary: Combining patient genetic data with functional in vivo assays in zebrafish reveals a possible role for DND1 in human male fertility.
HUMAN REPRODUCTION
(2023)
Review
Andrology
Csilla Krausz, Paulo Navarro-Costa, Martina Wilke, Frank Tuettelmann
Summary: Testing for AZoospermia Factor (AZF) deletions of the Y chromosome is crucial for diagnosing azoospermic and severely oligozoospermic men. This article summarizes recent advances in this field and provides an update on the external quality assessment program offered by the European Academy of Andrology (EAA) and EMQN CIC. The gold-standard method for detecting AZF deletions is a basic multiplex PCR reaction followed by a deletion extension analysis.
Meeting Abstract
Biochemistry & Molecular Biology
Godfried W. Van der Heijden, Manon Oud, Rytis Stakaitis, Ieva Golubickaite, Channah Gaasbeek, Nadja Rotte, Sabine Kliesch, Liliana Ramos, Kristian Almstrup, Miguel J. Xavier, Joris A. Veltman, Frank Tuettelmann
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Margot J. Wyrwoll, Manon S. Oud, Matthias Vockel, Sabine Kliesch, Corinna Friedrich, Frank Tuettelmann
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Hannah E. Smith, Manon S. Oud, Roos M. Smits, Francesco K. Mastrorosa, Giles S. Holt, Brendan J. Houston, Petra F. de Vries, Bilal K. S. Alobaidi, Lois Batty, Hadeel Ismail, Jackie Greenwood, Harsh Sheth, Aneta Mikulasova, Galuh Astuti, Christian Gilissen, Kevin McEleny, Helen Turner, Jonathan Coxhead, Simon Cockell, Didi D. M. Braat, Kathrin Fleischer, Kathleen W. M. D'Hauwers, E. Schaafsma, Don Conrad, Corinna Friedrich, Sabine Kliesch, Kenneth I. Aston, Antoni Riera-Escamilla, Csilla Krausz, Claudia Gonzaga-Jauregui, Mauro Santibanez-Koref, David J. Elliott, Lisenka E. L. M. Vissers, Frank Tuettelmann, Moira K. O'Bryan, Liliana Ramos, Miguel J. Xavier, Godfried W. van der Heijden, Joris A. Veltman
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jana Emich, Corinna Friedrich, Christina Burhoei, Thais Fenz Araujo, Ann-Christin Tewes, Susanne Ledig, Albrecht Roepke, Sabine Kliesch, Jorg Gromoll, Frank Tuettelmann
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Review
Obstetrics & Gynecology
Michael P. Rimmer, Ruth A. Howie, Richard A. Anderson, Christopher L. R. Barratt, Kurt T. Barnhart, Yusuf Beebeejaun, Ricardo Pimenta Bertolla, Siladitya Bhattacharya, Lars Bjorndahl, Pietro Bortoletto, Robert E. Brannigan, Astrid E. P. Cantineau, Ettore Caroppo, Barbara L. Collura, Kevin Coward, Michael L. Eisenberg, Christian De Geyter, Dimitrios G. Goulis, Ralf R. Henkel, Vu N. A. Ho, Alayman F. Hussein, Carin Huyser, Jozef H. Kadijk, Mohan S. Kamath, Shadi Khashaba, Yoshitomo Kobori, Julia Kopeika, Tansu Kucuk, Saturnino Lujan, Thabo Christopher Matsaseng, Raj S. Mathur, Kevin McEleny, Rod T. Mitchell, Ben W. Mol, Alfred M. Murage, Ernest H. Y. Ng, Allan Pacey, Antti H. Perheentupa, Stefan Du Plessis, Nathalie Rives, Ippokratis Sarris, Peter N. Schlegel, Majid Shabbir, Maciej Smiechowski, Venkatesh Subramanian, Sesh K. Sunkara, Basil C. Tarlarzis, Frank Tuttelmann, Andy Vail, Madelon van Wely, Monica H. Vazquez-Levin, Lan N. Vuong, Alex Y. Wang, Rui Wang, Armand Zini, Cindy M. Farquhar, Craig Niederberger, James M. N. Duffy
Summary: The study aims to develop a core outcome set for future male infertility research, as existing evidence from randomized trials may be difficult to interpret due to issues such as variation in outcome measures. Stakeholders will be invited to participate in the development process using consensus science methods, and a final core outcome set will be identified through a consensus development meeting.
HUMAN REPRODUCTION OPEN
(2022)