Article
Multidisciplinary Sciences
May E. Montasser, Cristopher V. Van Hout, Lawrence Miloscio, Alicia D. Howard, Avraham Rosenberg, Myrasol Callaway, Biao Shen, Ning Li, Adam E. Locke, Niek Verweij, Tanima De, Manuel A. Ferreira, Luca A. Lotta, Aris Baras, Thomas J. Daly, Suzanne A. Hartford, Wei Lin, Yuan Mao, Bin Ye, Derek White, Guochun Gong, James A. Perry, Kathleen A. Ryan, Qing Fang, Gannie Tzoneva, Evangelos Pefanis, Charleen Hunt, Yajun Tang, Lynn Lee, Carole Sztalryd-Woodle, Braxton D. Mitchell, Matthew Healy, Elizabeth A. Streeten, Simeon Taylor, Jeffrey R. O'Connell, Aris N. Economides, Giusy Della Gatta, Alan R. Shuldiner
Summary: Increased blood levels of LDL-C and fibrinogen are independent risk factors for cardiovascular disease. A missense variant in the B4GALT1 gene was associated with lower LDL-C and fibrinogen levels, as well as decreased risk of coronary artery disease. This suggests that targeting protein galactosylation could be a potential therapeutic approach for reducing cardiovascular disease risk.
Article
Biochemistry & Molecular Biology
Kelsey Jorgensen, Daisheng Song, Julien Weinstein, Obed A. Garcia, Laurel N. Pearson, Maria Inclan, Maria Rivera-Chira, Fabiola Leon-Velarde, Melisa Kiyamu, Tom D. Brutsaert, Abigail W. Bigham, Frank S. Lee
Summary: For over 10,000 years, Andeans have been living at high altitudes where the limited oxygen poses a challenge to human survival. Recent studies have discovered evidence of positive selection acting on the HIF2A locus in Andeans, which is associated with the hypoxia-inducible factor pathway. However, the specific mechanism by which this allele leads to altitude adaptation remains unknown. By analyzing the genomes of 46 Peruvian Andeans, researchers confirmed the presence of positive selection on HIF2A and identified a unique variation pattern surrounding the Andean-specific single nucleotide variant (SNV) rs570553380. This variant is associated with increased nitric oxide biosynthesis, as shown in a Peruvian Andean population living at high altitude.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Ayesha Zaka, Maha Yousaf, Shaheen Shahzad, Hadi Zahid Rao, Jia Nee Foo, Saima Siddiqi
Summary: 3M syndrome is a rare genetic familial disorder characterized by short stature, growth retardation, facial dysmorphism, skeletal abnormalities, fleshy protruding heels, and normal intelligence, caused by mutations in the CUL7, OBSL1 and CCDC8 genes. In this study, a novel homozygous missense variant of CUL7 has been identified in a consanguineous Pakistani family. Computational and experimental investigations reveal that this variant alters the protein's structure and interaction, providing useful information for drug development against this syndrome.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Neurosciences
Xiaona Wang, Daoqi Mei, Lingshan Gou, Shuai Zhao, Chao Gao, Jisheng Guo, Shuying Luo, Bin Guo, Zhigang Yang, Qi Wang, Tao Tan, Yaodong Zhang
Summary: This study identified a novel GRIN2B mutation in a patient with epilepsy and ID, and investigated the functional consequences of this mutation. The findings showed defects in the interactions of the mutated receptor with postsynaptic density, reduced delivery to the cell membrane, decreased glutamate affinity, and impaired surface expression of NMDA receptors in primary neurons.
Article
Genetics & Heredity
Xuefeng Xie, Mazhar Khan, Muhammad Zubair, Abbas Khan, Ranjha Khan, Jianteng Zhou, Yuanwei Zhang, Muzafar Said, Sher Ali Khan, Qamar Zaman, Ghulam Murtaza, Muzamil Ahmad Khan, Wei Liu, Xiaoning Hou, Huan Zhang, Bo Xu, Xiaohua Jiang, Shun Bai, Qinghua Shi
Summary: Non-obstructive azoospermia (NOA) is a major cause of male infertility, with the majority of cases remaining idiopathic. This study identified a novel missense mutation in the DND1 gene using whole-exome sequencing, and demonstrated its impact on male fertility through protein misfolding and weakened interaction with the crucial regulator NANOS2 in primordial germ cell development.
FRONTIERS IN GENETICS
(2022)
Article
Biology
Koji M. Nishiguchi, Fuyuki Miya, Yuka Mori, Kosuke Fujita, Masato Akiyama, Takashi Kamatani, Yoshito Koyanagi, Kota Sato, Toru Takigawa, Shinji Ueno, Misato Tsugita, Hiroshi Kunikata, Katarina Cisarova, Jo Nishino, Akira Murakami, Toshiaki Abe, Yukihide Momozawa, Hiroko Terasaki, Yuko Wada, Koh-Hei Sonoda, Carlo Rivolta, Tatsuhiko Tsunoda, Motokazu Tsujikawa, Yasuhiro Ikeda, Toru Nakazawa
Summary: Nishiguchi and colleagues identified three genetic variants within the EYS gene associated with retinitis pigmentosa using a genome-wide association study (GWAS). They demonstrated that one of these variants was pathogenic, able to explain an additional 7.0% of Japanese ARRP cases. Additionally, they found a high frequency variant potentially linked to the development of local genome therapeutics.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tifenn Desroziers, Gregoire Prevot, Aurore Coulomb, Valerie Nau, Florence Dastot-Le Moal, Philippe Duquesnoy, Melanie Hery, Aurelie Le Borgne, Serge Amselem, Marie Legendre, Nadia Nathan
Summary: This paper reports two related adults with pulmonary fibrosis due to a new homozygous SFTPB pathogenic variant. The variant induces aberrant splicing and almost complete loss of SP-B expression, leading to epithelial cell dysfunction and ILD. This finding highlights the importance of considering SFTPB pathogenic variants in atypical and/or early-onset forms of ILD, especially when a family history is present.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Sateesh Maddirevula, Seham Alameer, Nour Ewida, Mirta Mittelstedt Leal de Sousa, Magnar Bjoras, Cathrine Broberg Vagbo, Fowzan S. Alkuraya
Summary: ALKBH8 is a methyltransferase that methylates tRNAs by modifying the anticodon wobble uridine residue. A consanguineous family with two children carrying a novel missense variant in the methyltransferase domain confirms the pathogenicity of the variant and expands the understanding of molecular lesions in ALKBH8 associated with MRT71.
Article
Computer Science, Artificial Intelligence
Haicang Zhang, Michelle S. Xu, Xiao Fan, Wendy K. Chung, Yufeng Shen
Summary: Computational method gMVP based on graph attention neural networks is developed to accurately predict pathogenic missense variants, and it shows superior performance compared to other methods. The pooling of information and transfer learning capability of gMVP contribute to its improved interpretation of missense variants.
NATURE MACHINE INTELLIGENCE
(2022)
Article
Biochemistry & Molecular Biology
Stephanie Hilton, Matthias Christen, Thomas Bilzer, Vidhya Jagannathan, Tosso Leeb, Urs Giger
Summary: This study describes a clinically mild and slowly progressive muscular dystrophy in a family of Maine Coon crossbred cats. The cats exhibit marked structural changes in their muscles, but protein modeling suggests that the identified gene variant may not have a major impact on protein function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Vikas Pejaver, Alicia B. Byrne, Bing-Jian Feng, Kymberleigh A. Pagel, Sean D. Mooney, Rachel Karchin, Anne O'Donnell-Luria, Steven M. Harrison, Sean Tavtigian, Marc S. Greenblatt, Leslie G. Biesecker, Predrag Radivojac, Steven E. Brenner
Summary: The American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) provide recommendations for interpreting sequence variants, specifying the use of computational predictors as evidence for pathogenicity or benignity. However, the lack of quantitative support in the score intervals defined by tool developers and ACMG/AMP recommendations that require consensus of multiple predictors is addressed by a probabilistic framework proposed by the researchers. This framework is extended to computational predictors and introduces a new standard for converting tool scores to evidence strengths.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Richard Agren, Niels Geerdink, Han G. Brunner, Martin Paucar, Erik-Jan Kamsteeg, Kristoffer Sahlholm
Summary: A five-year-old girl with headache attacks and gait disturbances was found to have a new variant KCND3 c.838G>A, p.E280K in her father and sisters, but not in her mother and brother. KCND3 encodes voltage-gated potassium channel D3 (Kv4.3) and mutations have been associated with spinocerebellar ataxia type 19/22 (SCA19/22) and cardiac arrhythmias. The family members did not exhibit ataxia or parkinsonism, but both sisters showed mild developmental delay. Functional experiments showed that E280K affects channel activation and inactivation. Overall, E280K is associated with developmental delay but appears to be relatively benign.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Miranda Durkie, Christopher M. Watson, Peter Winship, Anne-Cecile Hogg, Rodney Nyanhete, Sharon Cooley, Manoj K. Valluru, Charles Shaw-Smith, Coralie Bingham, Mark Gilchrist, Janna Kenny, Genomics England Research Genomics England Res Consortium, Albert C. M. Ong
Summary: A study on a family revealed that variants in the PKD1 gene can cause early-onset polycystic kidney disease, and one specific variant is not associated with adult-onset disease. This finding is significant for screening purposes.
Article
Medicine, Research & Experimental
Sandra Andrea Salinas, Emily M. Mace, Matilde I. Conte, Chun Shik Park, Yu Li, Joshua I. Rosario-Sepulveda, Sanjana Mahapatra, Emily K. Moore, Evelyn R. Hernandez, Ivan K. Chinn, Abigail E. Reed, Barclay J. Lee, Alexander Frumovitz, Richard A. Gibbs, Jennifer E. Posey, Lisa R. Forbes Satter, Akaluck Thatayatikom, Eric J. Allenspach, Theodore G. Wensel, James R. Lupski, H. Daniel Lacorazza, Jordan S. Orange
Summary: NK cell deficiencies are a type of primary immune deficiency that affect the number, maturity, or function of NK cells. Patients with NKD are more susceptible to viral infections and may experience chronic, recurrent, and fatal infections. This study identified a damaging variant in the ELF4 gene as a potentially novel cause of NKD.
Article
Obstetrics & Gynecology
Ping Wang, Hong Liao, Quyou Wang, Hanbing Xie, He Wang, Mei Yang, Shanling Liu
Summary: This study identified a missense variant in the L1CAM gene in L1 syndrome patients, which was experimentally shown to affect cell function. The findings suggest a potential for prenatal diagnosis of fetuses with specific characteristics.
REPRODUCTIVE SCIENCES
(2022)
Article
Critical Care Medicine
Emilio Rodriguez-Ruiz, Ana Lopez-Lago, Rebeca Hernandez-Vaquero, Isabel Granja-Gomez, Ana Estany-Gestal, Ezequiel Alvarez, Miguel Garcia-Gonzalez, Jose L. Garcia-Allut
Review
Nutrition & Dietetics
Sol Carriazo, Maria Vanessa Perez-Gomez, Adrian Cordido, Miguel Angel Garcia-Gonzalez, Ana Belen Sanz, Alberto Ortiz, Maria Dolores Sanchez-Nino
Review
Urology & Nephrology
Luis Fernando Menezes, Gregory G. Germino
NATURE REVIEWS NEPHROLOGY
(2019)
Article
Microbiology
Marian Garcia-Nunez, Miguel Garcia-Gonzalez, Xavier Pomares, Concepcion Monton, Laura Millares, Sara Quero, Elena Prina, Oscar Asensio, Montserrat Bosque, Silvia Capilla, Oscar Cuevas, Eduard Monso
FRONTIERS IN MICROBIOLOGY
(2020)
Article
Biochemical Research Methods
Adrian Cordido, Eva Cernadas, Manuel Fernandez-Delgado, Miguel A. Garcia-Gonzalez
PLOS COMPUTATIONAL BIOLOGY
(2020)
Review
Medicine, General & Internal
Maria Garcia-Vence, Maria del Pilar Chantada-Vazquez, Ana Sosa-Fajardo, Rebeca Agra, Ana Barcia de la Iglesia, Alfonso Otero-Glez, Miguel Garcia-Gonzalez, Jose M. Cameselle-Teijeiro, Cristina Nunez, Juan J. Bravo, Susana B. Bravo
Summary: Tissue biopsies from patients are often FFPE-treated for long-term storage, which introduces crosslinks in proteins to improve stability. While these samples are suitable for immunohistochemical analysis, the crosslinks complicate protein extraction, necessitating specific protocols for different tissues to obtain high-quality proteins.
FRONTIERS IN MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Adrian Cordido, Marta Vizoso-Gonzalez, Miguel A. Garcia-Gonzalez
Summary: ARPKD is a rare disorder linked to the PKHD1 and DZIP1L genes, with research elucidating molecular pathways involved in disease progression. However, understanding of the function of ARPKD proteins and the disease's molecular mechanism remains incomplete.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Urology & Nephrology
Adrian Cordido, Laura Nunez-Gonzalez, Julio M. Martinez-Moreno, Olaya Lamas-Gonzalez, Laura Rodriguez-Osorio, Maria Vanessa Perez-Gomez, Diego Martin-Sanchez, Patricia Outeda, Marco Chiaravalli, Terry Watnick, Alessandra Boletta, Candido Diaz, Angel Carracedo, Ana B. Sanz, Alberto Ortiz, Miguel A. Garcia-Gonzalez
Summary: The TWEAK signaling pathway plays a crucial role in cystogenesis and cystic growth in ADPKD. High levels of TWEAK and Fn14 were observed in cysts from mouse ADPKD models and in urine/cystic fluid from ADPKD patients. Administration of TWEAK induced cystogenesis and worsened the phenotype, while anti-TWEAK antibodies slowed disease progression and improved outcomes.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Raquel Martinez-Pulleiro, Maria Garcia-Murias, Manuel Fidalgo-Diaz, Miguel Angel Garcia-Gonzalez
Summary: Alport syndrome is a rare genetic disease caused by mutations in collagen genes, primarily affecting the glomerular basement membrane of the kidney. It has renal involvement as the main manifestation, and may also present with hearing loss and ocular problems. There is no specific treatment currently available, but advances in genetic research and diagnosis are helping to better understand the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Laura Nunez-Gonzalez, Noa Carrera, Miguel A. Garcia-Gonzalez
Summary: Gitelman and Bartter syndromes are rare inherited diseases that result in electrolyte imbalances, especially in the nephron. Both syndromes share many similar clinical symptoms and the main treatment involves electrolyte supplementation and dietary changes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Fernando Gomez-Garcia, Raquel Martinez-Pulleiro, Noa Carrera, Catarina Allegue, Miguel A. Garcia-Gonzalez
Summary: This study discusses the genetic causes and phenotypic effects of genetic kidney diseases (GKDs) and describes and compares the application of site-specific nuclease systems (such as ZFNs, TALENs, and CRISPR-Cas9). It demonstrates that these systems can be used to edit the genes causing GKDs and generate models that reflect the genetic abnormalities, thus shedding light on many unknown aspects in the field of GKDs.
Article
Urology & Nephrology
Takeshi Terabayashi, Luis F. Menezes, Fang Zhou, Hongyi Cai, Peter J. Walter, Hugo M. Garraffo, Gregory G. Germino
Summary: The loss of Pkd1 does not disrupt peroxisome biogenesis or peroxisome-dependent metabolism.
Article
Urology & Nephrology
F. Z. Bensouilah, Dj. Chellat-Rezgoune, M. A. Garcia-Gonzalez, N. Carrera, N. Abadi, A. Dahdouh, D. Satta
AFRICAN JOURNAL OF UROLOGY
(2020)
Meeting Abstract
Transplantation
Lara Besada Cerecedo, Nisrine Arhda, Ana Maria Barcia de la Iglesia, Maria Garcia Murias, Noa Carrera Cachaza, Miguel Garcia Gonzalez
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2020)
Article
Developmental Biology
Sabela Da Silva-Alyarez, Olaya Lamas-Gonzalez, Alba Ferreiros, Patricia Gonzalez, Maria Gomez, Tomas Garcia-Caballero, Miguel Gonzalez Barcia, Miguel A. Garcia-Gonzalez, Manuel Collado
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
(2018)