Review
Obstetrics & Gynecology
M. D. Kilby
Summary: This paper reviews the role of NGS in investigating fetal malformations, emphasizing the importance of prospective case selection and informative pre-test counseling, as well as the crucial role of regulated laboratory sequencing and bioinformatic pathways in clinical practice.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2021)
Review
Genetics & Heredity
Alexandra Emms, James Castleman, Stephanie Allen, Denise Williams, Esther Kinning, Mark Kilby
Summary: Congenital malformations diagnosed by ultrasound screening have an underlying genetic cause in many cases. Next generation sequencing as a secondary prenatal genetic test offers additional diagnostic yield for congenital abnormalities potentially associated with genetic causes, especially in cases involving cardiac and neurological anomalies, large nuchal translucency, and non-immune fetal hydrops. The use of exome sequencing has shown significant incremental yield in single-system anomalies, making it a valuable tool for routine clinical care in fetuses with congenital abnormalities.
Review
Biochemistry & Molecular Biology
Esmat Karimi, Fatemeh Mahmoudian, Saul O. Lugo Reyes, Umair Ahmed Bargir, Manisha Madkaikar, Hasibe Artac, Araz Sabzevari, Na Lu, Gholamreza Azizi, Hassan Abolhassani
Summary: Patients with inborn errors of immunity (IEI) exhibit diverse clinical and immunological phenotypes, emphasizing the importance of accurate molecular diagnosis. Next generation sequencing has facilitated genetic examinations for rare inherited disorders, allowing a suitable molecular diagnosis for IEI patients. An efficient stepwise approach to molecular diagnosis of inborn errors of immunity has been suggested in light of current findings in the field.
MOLECULAR IMMUNOLOGY
(2021)
Article
Oncology
Tyler Shugg, Reynold C. Ly, Wilberforce Osei, Elizabeth J. Rowe, Caitlin A. Granfield, Ty C. Lynnes, Elizabeth B. Medeiros, Jennelle C. Hodge, Amy M. Breman, Bryan P. Schneider, S. Cenk Sahinalp, Ibrahim Numanagic, Benjamin A. Salisbury, Steven M. Bray, Ryan Ratcliff, Todd C. Skaar
Summary: This study assessed the accuracy of the Aldy computational method in extracting pharmacogenomics genotypes from whole genome sequencing (WGS) and whole exome sequencing (WES) data. The results showed that Aldy achieved over 99% accuracy in calling diplotypes for major pharmacogenes from both WGS and WES data, supporting its importance in clinical applications.
FRONTIERS IN ONCOLOGY
(2023)
Article
Gastroenterology & Hepatology
Narges Moradi, Solmaz Ohadian Moghadam, Siamak Heidarzadeh
Summary: Gastric cancer is a highly deadly and hard to diagnose disease. The use of next generation sequencing (NGS) techniques provides new opportunities for prognosis, diagnosis, and treatment of gastric cancer. This review discusses and compares current NGS techniques and commercial platforms used for gastric cancer diagnosis and treatment, and highlights the latest NGS-based studies. It also addresses the challenges of implementing NGS in clinical practice for gastric cancer.
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Developmental Biology
T. Yammine, N. Reynaud, H. Lejeune, F. Diguet, P. A. Rollat-Farnier, A. Labalme, I Plotton, C. Farra, D. Sanlaville, E. Chouery, C. Schluth-Bolard
Summary: Male infertility affects about 7% of the male population, with balanced chromosomal rearrangements being a well-established cause but with unclear underlying pathophysiological mechanisms. This study used a combination of cytogenetic and molecular techniques to identify candidate genes implicated in spermatogenesis defects in three male carriers of different balanced translocations. Breakpoints were characterized at the molecular level, revealing gene disruptions and variations that need further validation for their roles in male infertility. This study emphasizes the importance of combining cytogenetic and molecular techniques to investigate spermatogenesis disorders in patients with structural rearrangements on a genomic scale.
MOLECULAR HUMAN REPRODUCTION
(2021)
Article
Biochemistry & Molecular Biology
Valerio Benedetti, Rosalia Canzoneri, Andrea Perrelli, Carlo Arduino, Andrea Zonta, Alfredo Brusco, Saverio Francesco Retta
Summary: Cerebral Cavernous Malformation (CCM) is a genetic cerebrovascular disease that can cause seizures, neurological deficits, and fatal intracerebral hemorrhage. It is associated with loss-of-function mutations in three genes and may have additional genetic modifiers. A study in Italy identified pathogenic variants in CCM genes in 29% of CCM cases, as well as variants in other genes related to oxidative stress and inflammation.
Article
Immunology
Arun Kumar Arunachalam, Madhavi Maddali, Fouzia N. Aboobacker, Anu Korula, Biju George, Vikram Mathews, Eunice Sindhuvi Edison
Summary: This study characterized the clinical and genetic spectrum of PID patients in India, identifying BTK and IL12RB1 as the most common mutated genes, with autosomal recessive and X-linked recessive inheritance in 51.6% and 23.7% of patients, respectively. MSMD and IL12RB1 mutations were more common in this population compared to the Western world and the Middle East.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Review
Neurosciences
Behrouz Shademan, Cigir Biray Avci, Masoud Nikanfar, Alireza Nourazarian
Summary: The NGS method is crucial for identifying genetic causes of neurodegenerative diseases like Alzheimer's and Parkinson's by quickly and accurately diagnosing them. With its ability to cater to individual genome variations, NGS has transformed personalized medicine and treatment strategies. However, the NGS method also has its own limitations.
NEUROMOLECULAR MEDICINE
(2021)
Article
Immunology
Xiaolei Zhang, Yixue Wang, Daly Pen, Jing Liu, Qinhua Zhou, Yao Wang, Huaqing Zhong, Tingyan Liu, Weiming Chen, Bingbing Wu, Yang Zhou, Chuanqing Wang, Xiangyu Li, Fangyou Yu, Xiaochuan Wang, Guoping Lu, Gangfeng Yan
Summary: This study reports a rare case of MHC II deficiency in a 117-day-old boy, whose diagnosis was obtained mainly through NGS. The case highlights the potential importance of NGS in diagnosing unexplained infection and illness, and the accuracy of pathogen identification can be improved by combining conventional detection techniques with mNGS.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Medicine, General & Internal
Bianca Tesi, Catherine Boileau, Kym M. Boycott, Guillaume Canaud, Mark Caulfield, Daniela Choukair, Sue Hill, Malte Spielmann, Anna Wedell, Valtteri Wirta, Ann Nordgren, Anna Lindstrand
Summary: Molecular diagnostics plays a crucial role in tailoring individual treatment and care based on molecular data. Genome sequencing (GS) is emerging as the primary method for precision diagnostics in rare diseases, due to its improved diagnostic yield and ability to detect a broad range of genetic aberrations. By integrating precision medicine into clinical practice, GS can accelerate targeted drug development and improve patient management in rare diseases.
JOURNAL OF INTERNAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Natsuko Aida, Akiko Saito, Toshifumi Azuma
Summary: The development of next-generation sequencing (NGS) has greatly improved the speed and capacity of genetic analysis, expanding its applications to include genome, epigenome, metagenome, and transcriptome analyses. Bone tissue, as a crucial unit supporting the body, is susceptible to genetic diseases. The relationship between age-related bone fragility and genetic factors has recently gained attention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Claudia Saglia, Valeria Bracciama, Luca Trotta, Fiorenza Mioli, Angelo Corso Faini, Giulia Margherita Brach Del Prever, Silvia Kalantari, Maria Luca, Carmelo Maria Romeo, Caterina Scolari, Licia Peruzzi, Pier Luigi Calvo, Alessandro Mussa, Roberta Fenoglio, Dario Roccatello, Claudio Alberti, Diana Carli, Antonio Amoroso, Silvia Deaglio, Tiziana Vaisitti
Summary: This study evaluated the utility of NGS data re-analysis for patients with inconclusive or negative genetic test results. The results showed that re-analysis can lead to the identification of new causative variants or the reclassification of existing variants, which has significant implications for patient management.
BMC MEDICAL GENOMICS
(2023)
Article
Genetics & Heredity
Kelly Schoch, Cecilia Esteves, Anna Bican, Rebecca Spillmann, Heidi Cope, Allyn McConkie-Rosell, Nicole Walley, Liliana Fernandez, Jennefer N. Kohler, Devon Bonner, Chloe Reuter, Nicholas Stong, John J. Mulvihill, Donna Novacic, Lynne Wolfe, Ayat Abdelbaki, Camilo Toro, Cyndi Tifft, May Malicdan, William Gahl, Pengfei Liu, John Newman, David B. Goldstein, Jason Hom, Jacinda Sampson, Matthew T. Wheeler, Joy Cogan, Jonathan A. Bernstein, David R. Adams, Alexa T. McCray, Vandana Shashi
Summary: The study evaluates the contributions of UDN clinical sites in diagnosing patients with undiagnosed diseases, demonstrating significant improvements in diagnosis rates and new disease gene discoveries.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Elizabeth K. Baker, Elizabeth A. Ulm, Alyce Belonis, Diana S. Brightman, Barbara E. Hallinan, Nancy D. Leslie, Alexander G. Miethke, Marissa Vawter-Lee, Yaning Wu, Loren D. M. Pena
Summary: Exome sequencing (ES) is a clinically available technique that provides an unbiased and high-throughput sequencing platform for patients with symptoms believed to have a genetic cause. Recent studies have shown that a post-exome evaluation, including clinical re-phenotyping, functional studies, and variant reevaluation, can significantly increase the diagnostic yield.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Sofia Barbosa-Gouveia, Maria E. Vazquez-Mosquera, Emiliano Gonzalez-Vioque, Alvaro Hermida-Ameijeiras, Laura L. Valverde, Judith Armstrong-Moron, Maria del Carmen Fons-Estupina, Liesbeth T. Wintjes, Antonia Kappen, Richard J. Rodenburg, Maria L. Couce
Summary: This study describes a case of an infant with a novel AGK variant, showing mitochondrial dysfunction, decreased electron flow in the respiratory chain, and reduced activity of OXPHOS complexes. Experimental validation in vitro elucidated the molecular mechanism underlying the pathogenicity of the variant.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Maria E. Vazquez-Mosquera, Emiliano Gonzalez-Vioque, Sofia Barbosa-Gouveia, Diego Bellido-Guerrero, Cristina Tejera-Perez, Miguel A. Martinez-Olmos, Antia Fernandez-Pombo, Luis A. Castano-Gonzalez, Roi Chans-Gerpe, Maria L. Couce
Summary: Transcriptomic analysis shows diagnostic utility in patients with suspected MODY, even though only some genes exhibit expression alterations in peripheral blood.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Medicine, General & Internal
Sofia Barbosa-Gouveia, Maria Eugenia Vazquez-Mosquera, Emiliano Gonzalez-Vioque, Alvaro Hermida-Ameijeiras, Paula Sanchez-Pintos, Maria Jose de Castro, Soraya Ramiro Leon, Belen Gil-Fournier, Cristina Dominguez-Gonzalez, Ana Camacho Salas, Luis Negrao, Isabel Fineza, Francisco Laranjeira, Maria Luz Couce
Summary: Neuromuscular diseases are genetically heterogeneous, making diagnosis challenging. In this study, comprehensive gene-panel analysis and next-generation sequencing were used to analyze 268 patients with suspected inherited neuromuscular disorders. The addition of genes to the panel increased the diagnostic rate exponentially, with an overall rate of 36%. Most diagnoses were muscular dystrophies/myopathies and peripheral nerve diseases. The most common causative genes were TTN, RYR1, and ANO5.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Nutrition & Dietetics
Ainara Cano, Carlos Alcalde, Amaya Belanger-Quintana, Elvira Canedo-Villarroya, Leticia Ceberio, Silvia Chumillas-Calzada, Patricia Correcher, Maria Luz Couce, Dolores Garcia-Arenas, Igor Gomez, Tomas Hernandez, Elsa Izquierdo-Garcia, Damaris Martinez Chicano, Montserrat Morales, Consuelo Pedron-Giner, Estrella Petrina Jauregui, Luis Pena-Quintana, Paula Sanchez-Pintos, Juliana Serrano-Nieto, Maria Unceta Suarez, Isidro Vitoria Minana, Javier de las Heras
Summary: The study found that inadequate intake of vitamin C and folate is common in patients with hereditary fructose intolerance (HFI). While supplementation with vitamin C is positively correlated with plasma levels, a significant number of HFI patients who do not receive supplementation still experience vitamin C deficiency. Further research is needed to establish optimal doses of vitamin C and the necessity of folate supplementation in HFI.
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Alejandro Soriano-Sexto, Diana Gallego, Fatima Leal, Natalia Castejon-Fernandez, Rosa Navarrete, Patricia Alcaide, Maria L. Couce, Elena Martin-Hernandez, Pilar Quijada-Fraile, Luis Pena-Quintana, Raquel Yahyaoui, Patricia Correcher, Magdalena Ugarte, Pilar Rodriguez-Pombo, Belen Perez
Summary: This study utilized a personalized multi-omics pipeline and functional genomics to aid in the genetic diagnosis of six unsolved cases. Eight novel variants were identified and their pathogenic effects were confirmed. This highlights the importance of combining different omics technologies and functional analysis in solving challenging clinical cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Elena Martin-Hernandez, Pilar Quijada-Fraile, Patricia Correcher, Silvia Meavilla, Paula Sanchez-Pintos, Javier de las Heras Montero, Javier Blasco-Alonso, Lucy Dougherty, Ana Marquez, Luis Pena-Quintana, Elvira Canedo, Maria Concepcion Garcia-Jimenez, Pedro Juan Moreno Lozano, Mercedes Murray Hurtado, Maria Camprodon Gomez, Delia Barrio-Carreras, Mariela de los Santos, Mireia del Toro, Maria L. Couce, Isidro Vitoria Minana, Montserrat Morales Conejo, Marcello Bellusci
Summary: The study demonstrates the safety and efficacy of directly switching from other nitrogen scavengers to GPB in clinical practice, showing improved metabolic control, reduced hyperammonemic crisis rate, and related adverse effects compared to previous treatments.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Maria del Pilar Chantada-Vazquez, Susana B. Bravo, Sofia Barbosa-Gouveia, Jose V. Alvarez, Maria L. Couce
Summary: Inherited metabolic disorders (IMDs) are rare medical conditions caused by genetic defects that affect the body's metabolism. Early diagnosis and understanding of the disease are crucial, and proteomics and tandem mass spectrometry (MS/MS) have emerged as valuable tools for studying IMDs. Proteomics can aid in the identification of biomarkers, early diagnosis, and better understanding of the underlying pathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Nestor Vazquez-Agra, Silvia Fernandez-Crespo, Ana -Teresa Marques-Afonso, Anton Cruces-Sande, Sofia Barbosa-Gouveia, Miguel-Angel Martinez-Olmos, Alvaro Hermida-Ameijeiras
Summary: This study evaluated the influence of metabolic control on classical cardiovascular risk factors in adult patients with Phenylketonuria (PKU). The results showed that high phenylalanine levels and fluctuations were associated with weight gain, increased waist circumference, and lipid profile abnormalities. Therefore, systematic cardiovascular risk assessments and comprehensive monitoring of phenylalanine levels may help prevent or delay cardiovascular disease in PKU patients.
Article
Medicine, General & Internal
Sofia Barbosa-Gouveia, Silvia Fernandez-Crespo, Hector Lazare-Iglesias, Arturo Gonzalez-Quintela, Nestor Vazquez-Agra, Alvaro Hermida-Ameijeiras
Summary: In this study, a case of a 59-year-old male patient with typical features of Tangier disease was described, and a likely pathogenic variant in the ABCA1 gene was identified through whole-exome sequencing. Bioinformatics and genomics analysis were used to predict the impact of the variant on the protein structure and function, highlighting the importance of integrating these approaches to understand the genotype-phenotype relationship and functional consequences of genetic variations.
JOURNAL OF CLINICAL MEDICINE
(2023)
Correction
Nutrition & Dietetics
Ainara Cano, Carlos Alcalde, Amaya Belanger-Quintana, Elvira Canedo-Villarroya, Leticia Ceberio, Silvia Chumillas-Calzada, Patricia Correcher, Maria Luz Couce, Dolores Garcia-Arenas, Igor Gomez, Tomas Hernandez, Elsa Izquierdo-Garcia, Damaris Martinez Chicano, Montserrat Morales, Consuelo Pedron-Giner, Estrella Petrina Jauregui, Luis Pena-Quintana, Paula Sanchez-Pintos, Juliana Serrano-Nieto, Maria Unceta Suarez, Isidro Vitoria Minana, Javier de las Heras
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2023)
Article
Nutrition & Dietetics
Isidro Vitoria-Minana, Maria-Luz Couce, Domingo Gonzalez-Lamuno, Monica Garcia-Peris, Patricia Correcher-Medina
Summary: This study designed a spreadsheet to calculate the required amounts of a special amino acid formula and human milk for infants with inborn errors of metabolism of amino acids and proteins. The spreadsheet takes into consideration the infant's metabolic status and individual requirements, and can also calculate the necessary volume of expressed milk in certain conditions.
Article
Endocrinology & Metabolism
Silvia Santos Monteiro, Tiago da Silva Santos, Liliana Fonseca, Guilherme Assuncao, Ana M. Lopes, Diana B. Duarte, Ana Rita Soares, Francisco Laranjeira, Isaura Ribeiro, Eugenia Pinto, Sonia Rocha, Sofia Barbosa Gouveia, Maria Eugenia Vazquez-Mosquera, Maria Joao Oliveira, Teresa Borges, Maria Helena Cardoso
Summary: This study describes a Portuguese cohort of individuals with suspected monogenic diabetes who underwent genetic testing for MODY-causing genes. The results emphasize the importance of genetic testing in the diagnosis of MODY and the establishment of personalized treatment and follow-up strategies.
ACTA DIABETOLOGICA
(2023)
Article
Biochemistry & Molecular Biology
Jorge Moreda-Pineiro, Jose A. Cocho, Maria Luz Couce, Antonio Moreda-Pineiro, Pilar Bermejo-Barrera
Summary: Trace elements in dried blood spots from newborns were analyzed to classify healthy newborns and newborns with metabolic disorders. Unsupervised and supervised pattern recognition techniques showed a clear tendency to separate these two groups, with over 90% accuracy in classification achieved by supervised techniques. Additionally, essential elements in blood spots were found to be correlated with specific amino acids linked to metabolic disorders.