Article
Cell Biology
Sayantan Nandi, Saravanakkumar Chennappan, Yannik Andrasch, Miray Fidan, Melanie Engler, Mubashir Ahmad, Jan P. Tuckermann, Martin Zenker, Ion Cristian Cirstea
Summary: RAS GTPases are important proteins that regulate cellular signaling and control various biological processes. Mutations in RAS genes have significant effects on cellular homeostasis and can result in cancer or developmental disorders. One specific disorder caused by germline mutations in the HRAS gene is Costello syndrome, which is characterized by cardiac anomalies, growth impairments, cognitive impairments, craniofacial anomalies, and increased cancer susceptibility. A mouse model of Costello syndrome with a specific Hras germline mutation was used to study the bone phenotype. The results showed that the Hras mutation induced bone loss in mice, and this was associated with an increased number of osteoclasts. Inhibition of certain signaling pathways reduced mutant osteoclast differentiation. These findings suggest that Hras plays a role in bone homeostasis and that increased osteoclastogenesis due to the Hras mutation contributes to bone loss in Costello syndrome.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Genetics & Heredity
Wen Qian, Meijie Zhang, Hequn Huang, Yihe Chen, Gajin Park, Ni Zeng, Yueyue Li, Qian Lu, Dan Luo
Summary: This article reports a patient with Costello syndrome (CS) with a p.G12D variant in the HRAS gene, presenting with special but mild manifestations. Previous cases with the G12D variant showed that patients died within three months after birth. These patients exhibited typical features such as facial characteristics, failure to thrive, skin and cardiac abnormalities.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Cell Biology
William E. Tidyman, Alice F. Goodwin, Yoshiko Maeda, Ophir D. Klein, Katherine A. Rauen
Summary: Costello syndrome (CS) is a congenital disorder caused by mutations in the Ras/MAPK pathway, leading to hypotonia as a prominent feature. A mouse model with activating Hras(G12V) allele revealed that hypotonia in CS is primarily due to inhibition of muscle development and myofiber formation, resulting in reduced muscle mass and strength.
DISEASE MODELS & MECHANISMS
(2022)
Article
Obstetrics & Gynecology
Chih-Ping Chen, Chen-Yu Chen, Schu-Rern Chern, Shin-Wen Chen, Fang-Tzu Wu, Wen-Lin Chen, Meng-Shan Lee, Wayseen Wang
Summary: This case report presents prenatal diagnosis of recurrent mosaic ring chromosome 13 of maternal origin. The discovery of r(13) and a deletion in chromosome 13q31.3q34 in the fetus led to termination of pregnancy and delivery of a malformed baby. Polymorphic DNA marker analysis confirmed the maternal origin of the abnormal chromosome.
TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
(2021)
Article
Developmental Biology
Peter K. Nicholls, David C. Page
Summary: Germ cells commit to gametogenesis after colonizing the gonads, and germ cell tumors may originate from cells that failed to undergo germ cell determination. The diversity of cell types in these tumors reflects the developmental potential of migratory PGCs.
Article
Genetics & Heredity
Koki Nagai, Tetsuya Niihori, Nobuhiko Okamoto, Akane Kondo, Kenichi Suga, Tomoko Ohhira, Yasunobu Hayabuchi, Yukako Homma, Ryuji Nakagawa, Toshinobu Ifuku, Taiki Abe, Takeshi Mizuguchi, Naomichi Matsumoto, Yoko Aoki
Summary: Costello syndrome is an autosomal dominant disorder characterized by distinctive facial features, hypertrophic cardiomyopathy, skeletal abnormalities, intellectual disability, and predisposition to cancers, with germline variants in HRAS being identified in patients. In this study, it was found that small in-frame duplications within the HRAS gene enhance the activation of the ERK pathway, resulting in developmental abnormalities in zebrafish embryos or patients with Costello syndrome.
Article
Dermatology
Hiroto Ono, Reimon Yamaguchi, Minako Arai, Sumihito Togi, Hiroki Ura, Yo Niida, Akira Shimizu
Summary: Schimmelpenning-Feuerstein-Mims syndrome (SFMS) is an epidermal nevus disease characterized by craniofacial nevus sebaceous and extracutaneous anomalies. Genetic studies have identified somatic mutations in HRAS, KRAS, and NRAS genes. This case report describes a 48-year-old man with clinical features suggesting SFMS, and a pathogenic HRAS variant NM_005343.4:c.34G > A p.(Gly12Ser) identified in nevus sebaceous skin but not blood, indicating somatic mosaicism. This study highlights the presence of HRAS p.(Gly12Ser) mutation in SFMS and discusses the role of RAS mutations in somatic RASopathies.
JOURNAL OF DERMATOLOGY
(2023)
Article
Genetics & Heredity
Ting Bai, Ying Shen, Yanting Yang, Siyu Dai, Hongqian Liu
Summary: This article reports a case of fetal CHARGE syndrome (CS) with a CHD7 variant inherited from maternal CHD7 gonosomal mosaicism. The study emphasizes the importance of clinical analysis in accurately determining the parents' status and has vital implications for evaluating the recurrence risk for genetic counseling.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Dermatology
Jianying Liang, Yifeng Guo, Zhiyong Lu, Hong Yu, Liangcai Wu, Zhirong Yao
Summary: Disease characteristics vary with HRAS mutations, as shown in two cases: one with a mutation causing a nevus and the other with familial Costello syndrome. The potential mosaicism in the father highlights the genetic risks associated with familial mutations.
JOURNAL OF DERMATOLOGY
(2022)
Article
Genetics & Heredity
Aude Beyens, Charlotte Lietaer, Kathleen Claes, Elfride De Baere, Marleen Goeteyn, Bob Lerut, Hannes Syryn, Olivier Vanakker, Joni Van der Meulen, Lieve Vanwalleghem, Bert Callewaert
Summary: Epidermal nevus syndrome (ENS) is a heterogeneous group of neurocutaneous syndromes characterized by the presence of epidermal nevi and various extracutaneous manifestations. This report reveals the association of HRAS-related ENS with auricular atresia and highlights the possibility of mosaic HRAS variation as the underlying cause of nevus comedonicus. It extends our understanding of the pleiotropic effects of mosaic pathogenic variants in HRAS affecting different cell lineages.
Article
Environmental Sciences
Bauke Debo, Marlies Van Loocke, Katya De Groote, Els De Leenheer, Martine Cools
Summary: Children with sex chromosomal mosaicism involving Y-derived material may exhibit a range of Turner syndrome features, with differences in age of diagnosis, skeletal maturation, and growth hormone therapy response between boys and girls. Both boys and girls with this condition show similar prevalence of cardiac, ear-nose-throat, and renal issues, but there is a significant difference in presence of premalignant germ cell tumors, with none in males and 42.9% in females.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Genetics & Heredity
Tanja Frey, Ivan Ivanovski, Angela Bahr, Markus Zweier, Julia Laube, Isabelle Luchsinger, Katharina Steindl, Anita Rauch
Summary: Costello syndrome is a severe neurodevelopmental disorder caused by activating variants in HRAS. We report a unique and attenuated phenotype in six individuals with the HRAS variant c.176C>T p.(Ala59Gly), which has not been reported before as a germline variant. These individuals show ectodermal anomalies and mild features of a RASopathy, similar to patients with a Noonan syndrome-like disorder. Our findings suggest a distinct HRAS-related RASopathy for patients carrying HRAS variants affecting codons 58, 59, 60.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Oncology
Katarina Rejlekova, Katarina Kalavska, Marek Makovnik, Nikola Hapakova, Michal Chovanec, Valentina De Angelis, Jana Obertova, Patrik Palacka, Zuzana Sycova-Mila, Jozef Mardiak, Michal Mego
Summary: This retrospective study aimed to identify the risk factors associated with the development of choriocarcinoma syndrome (CS) in high-risk germ cell tumor (GCT) patients. The results showed that ECOG PS ≥ 2 and metastatic lung involvement ≥ 50% were independently associated with CS development.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Yidong Chen, Yuan Gao, Jialin Jia, Liang Chang, Ping Liu, Jie Qiao, Fuchou Tang, Lu Wen, Jin Huang
Summary: The discovery of embryonic cell-free DNA in spent embryo culture media has provided hope for noninvasive preimplantation genetic testing. However, the cellular origins of this DNA are not well understood, and methods for detecting maternal DNA contamination are limited. This study used whole-genome DNA methylation sequencing to identify the sources of cell-free DNA in spent embryo culture media, providing insights into noninvasive preimplantation genetic testing.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Joseph A. Moore, Rebecca S. Slack, Michael J. Lehner, Matthew T. Campbell, Amishi Y. Shah, Miao Zhang, Charles C. Guo, John F. Ward, Jose A. Karam, Christopher G. Wood, Louis L. Pisters, Shi-Ming Tu
Summary: Very late recurrence of testicular germ cell tumors is a rare event, occurring in about 1% of patients and associated with poor prognosis. Patients who did not undergo surgery to remove residual disease after chemotherapy are more likely to develop somatic transformation and die from the late recurrence.
Article
Genetics & Heredity
Marcello Niceta, Emilia Stellacci, Karen W. Gripp, Giuseppe Zampino, Maria Kousi, Massimiliano Anselmi, Alice Traversa, Andrea Ciolfi, Deborah Stabley, Alessandro Bruselles, Viviana Caputo, Serena Cecchetti, Sabrina Prudente, Maria T. Fiorenza, Carla Boitani, Nicole Philip, Dmitriy Niyazov, Chiara Leoni, Takaya Nakane, Kim Keppler-Noreuil, Stephen R. Braddock, Gabriele Gillessen-Kaesbach, Antonio Palleschi, Philippe M. Campeau, Brendan H. L. Lee, Celio Pouponnot, Lorenzo Stella, Gianfranco Bocchinfuso, Nicholas Katsanis, Katia Sol-Church, Marco Tartaglia
AMERICAN JOURNAL OF HUMAN GENETICS
(2015)
Article
Genetics & Heredity
Karen W. Gripp, Katia Sol-Church, Patroula Smpokou, Gail E. Graham, David A. Stevenson, Heather Hanson, David H. Viskochil, Laura C. Baker, Bridget Russo, Nick Gardner, Deborah L. Stabley, Verena Kolbe, Georg Rosenberger
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2015)
Article
Genetics & Heredity
Karen W. Gripp, Katherine M. Robbins, Brandon S. Sheffield, Anna F. Lee, Millan S. Patel, Stephen Yip, Daniel Doyle, Deborah Stabley, Katia Sol-Church
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2016)
Article
Genetics & Heredity
Katherine M. Robbins, Deborah L. Stabley, Jennifer Holbrook, Rebecca Sahraoui, Alexa Sadreameli, Katrina Conard, Laura Baker, Karen W. Gripp, Katia Sol-Church
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2016)
Article
Genetics & Heredity
Karen W. Gripp, Kimberly A. Aldinger, James T. Bennett, Laura Baker, Jessica Tusi, Nina Powell-Hamilton, Deborah Stabley, Katia Sol-Church, Andrew E. Timms, William B. Dobyns
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2016)
Article
Urology & Nephrology
Yanping Wang, Jin Li, Thomas F. Kolon, Alicia Olivant Fisher, T. Ernesto Figueroa, Ahmad H. BaniHani, Jennifer A. Hagerty, Ricardo Gonzalez, Paul H. Noh, Rosetta M. Chiavacci, Kisha R. Harden, Debra J. Abrams, Deborah Stabley, Cecilia E. Kim, Katia Sol-Church, Hakon Hakonarson, Marcella Devoto, Julia Spencer Barthold
Article
Clinical Neurology
Deborah L. Stabley, Jennifer Holbrook, Ashlee W. Harris, Kathryn J. Swoboda, Thomas O. Crawford, Katia Sol-Church, Matthew E. R. Butchbach
NEUROMUSCULAR DISORDERS
(2017)
Article
Oncology
Donna M. Cartledge, Katherine M. Robbins, Katherine M. Drake, Rachel Sternberg, Deborah L. Stabley, Karen W. Gripp, E. Anders Kolb, Katia Sol-Church, Andrew D. Napper
FRONTIERS IN ONCOLOGY
(2017)
Article
Genetics & Heredity
Amy J. Lacroix, Deborah Stabley, Rebecca Sahraoui, Margaret P. Adam, Michele Mehaffey, Kelly Kernan, Candace T. Myers, Carrie Fagerstrom, George Anadiotis, Yassmine M. Akkari, Katherine M. Robbins, Karen W. Gripp, Wagner Ar Baratela, Michael B. Bober, Angela L. Duker, Dan Doherty, Jennifer C. Dempsey, Daniel G. Miller, Martin Kircher, Michael J. Bamshad, Deborah A. Nickerson, Heather C. Mefford, Katia Sol-Church
AMERICAN JOURNAL OF HUMAN GENETICS
(2019)
Article
Genetics & Heredity
Amy R. Shikany, Laura Baker, Deborah L. Stabley, Katherine Robbins, Daniel Doyle, Karen W. Gripp, K. Nicole Weaver
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Biochemistry & Molecular Biology
Karen W. Gripp, Laura Baker, Katherine M. Robbins, Deborah L. Stabley, Gary A. Bellus, Verena Kolbe, Theresa Nauth, Georg Rosenberger
EUROPEAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Genetics & Heredity
Deborah L. Stabley, Jennifer Holbrook, Mena Scavina, Thomas O. Crawford, Kathryn J. Swoboda, Katherine M. Robbins, Matthew E. R. Butchbach
Summary: Proximal spinal muscular atrophy (SMA) is an early-onset motor neuron disease caused by deletion or disabling mutations of survival motor neuron 1 (SMN1) and affected by the copy number of paralog SMN2. Array digital PCR (dPCR) can accurately and reliably measure SMN1 and SMN2 copy numbers and detect gene conversion events and partial deletions of SMN1. In SMA, higher SMN2 copy numbers are associated with milder disease severity.
Article
Pediatrics
Diksha Shrestha, George Xiangyun Ye, Deborah Stabley, Suhita Gayen nee Betal, Yan Zhu, Lisa Glazewski, Jennifer Holbrook, Meharpreet Sethi, Anne Hesek, Thomas H. Shaffer, Zubair H. Aghai, Sankar Addya, Deepthi Alapati
Summary: The study found that lung inflammation in preterm infants with BPD during the perinatal period leads to short- and long-term dysregulation of genes associated with pulmonary-specific immune cells, potentially increasing the risk of respiratory morbidities associated with environmental pathogens in children and adults with BPD.
PEDIATRIC RESEARCH
(2021)
Article
Genetics & Heredity
David D. Schwartz, Jennifer M. Katzenstein, Eric J. Highley, Deborah L. Stabley, Katia Sol-Church, Karen W. Gripp, Marni E. Axelrad
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2017)
Article
Genetics & Heredity
Debora Bertola, Michelle Buscarilli, Deborah L. Stabley, Laura Baker, Daniel Doyle, Dennis W. Bartholomew, Katia Sol-Church, Karen W. Gripp
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2017)