Article
Oncology
Hafdis T. Helgadottir, Jessada Thutkawkorapin, Anna Rohlin, Margareta Nordling, Kristina Lagerstedt-Robinson, Annika Lindblom
Summary: Identifying pathogenic variants remains challenging despite a strong history of CRC within families. Some rare high-risk mutations may cumulatively contribute to the occurrence of CRC in these families.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Review
Oncology
Francesco Passiglia, Umberto Malapelle, Nicola Normanno, Carmine Pinto
Summary: Pharmacological inhibition of EGFRex20 insertions offers new treatment opportunities for advanced NSCLC patients. Drugs like amivantamab and mobocertinib have received regulatory approval. NGS-based genotyping is considered the gold standard approach for profiling advanced NSCLC patients.
CANCER TREATMENT REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Ayaz Khan, Shixiong Tian, Muhammad Tariq, Sheraz Khan, Muhammad Safeer, Naimat Ullah, Nazia Akbar, Iram Javed, Mahnoor Asif, Ilyas Ahmad, Shahid Ullah, Humayoon Shafique Satti, Raees Khan, Muhammad Naeem, Mahwish Ali, John Rendu, Julien Faure, Klaus Dieterich, Xenia Latypova, Shahid Mahmood Baig, Naveed Altaf Malik, Feng Zhang, Tahir Naeem Khan, Chunyu Liu
Summary: This study used next-generation sequencing to accurately diagnose hereditary neurological disorders in 11 unrelated Pakistani families. Through genome sequencing, disease-causing genetic variants were identified, including four novel variants. This study not only expands the mutational spectrum of neurological disorders, but also has implications for genetic testing in other populations with these disorders.
MOLECULAR GENETICS AND GENOMICS
(2022)
Article
Medicine, Legal
Jennifer Fadoni, Agostinho Santos, Laura Caine
Summary: This study investigated the genetic variants present in young sudden cardiac death (SCD) victims with hypertrophic cardiomyopathy (HCM) characteristics. Through next-generation sequencing, pathogenic or likely pathogenic variants were identified in 37.5% of the victims, mainly in the MYBPC3 and MYH7 genes. The molecular autopsy of SCD victims contributes to the identification of a cause of death and can be used for prevention of SCD through family screening.
INTERNATIONAL JOURNAL OF LEGAL MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Vera Belova, Anna Shmitko, Anna Pavlova, Robert Afasizhev, Valery Cheranev, Anastasia Tabanakova, Natalya Ponikarovskaya, Denis Rebrikov, Dmitriy Korostin
Summary: This study compared the newly released Agilent SureSelect Human All Exon v8 probe set with the previous v7 set, finding that the v8 probe set can more accurately call SNVs and indels on the same target regions, indicating better data quality.
Article
Biochemical Research Methods
Alejandro Rubio, Juan Jimenez, Antonio J. Perez-Pulido
Summary: Bacterial genomes provide valuable data for understanding the complete set of genes of a species. By analyzing multiple bacterial strains, shared genes and strain-specific genes can be identified. However, current computational gene finders may miss some existing genes. This study estimated the selective pressure on genes in the Acinetobacter baumannii pangenome and found that most genes are under negative selection, but a subset showed values compatible with positive selection, which may be related to acquisition of new functions.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Microbiology
N. V. Patin, K. D. Goodwin
Summary: The study compared long- and short-read sequencing of marine metagenomes, finding a wide range of long-read metagenome qualities and minimal improvements to microbiome analyses. However, long reads were able to generate draft genomes of eukaryotic algal species and provide full-length marker gene sequences of zooplankton species. This suggests that long-read sequencing can provide greater genetic insight into the wide diversity of eukaryotic phyto- and zooplankton present in marine environments.
Article
Microbiology
Yi Zhang, Xuan Lu, Liang V. Tang, Linghui Xia, Yu Hu
Summary: The new technique of nanopore-targeted sequencing (NTS) can rapidly and accurately detect pathogenic microorganisms and is highly suitable for patients with serious infections. The study demonstrates that NTS can guide anti-infection treatment, significantly improve patients' conditions, and reduce infection-related mortality.
Article
Genetics & Heredity
Shujuan Yan, Fang Fu, Ru Li, Qiuxia Yu, Fucheng Li, Hang Zhou, You Wang, Ruibin Huang, Chunling Ma, Fei Guo, Dan Wang, Xin Yang, Jin Han, Tingyin Lei, Dongzhi Li, Can Liao
Summary: This retrospective study evaluated the use of exome sequencing (ES) for identifying genetic causes of congenital orofacial clefts (OFCs) in fetuses. The study found that clinically significant variants were identified in 11.2% of fetuses, with no significant difference between isolated cleft lip and/or palate (CL/CP) and syndromic CL/CP groups. The study highlights the importance of ES in prenatal diagnosis and expands our understanding of the genetic underpinnings of OFCs.
FRONTIERS IN GENETICS
(2023)
Article
Clinical Neurology
F. Bisulli, C. Rinaldi, T. Pippucci, R. Minardi, S. Baldassari, C. Zenesini, B. Mostacci, M. Fanella, P. Avoni, V Menghi, L. Caporali, L. Muccioli, P. Tinuper, L. Licchetta
Summary: Epilepsy with Auditory Features (EAF) is a focal epilepsy syndrome with mainly unknown genetic causes. LGI1, RELN, SCN1A, and DEPDC5 have been identified as genetic causes in some cases, but the overall genetic background of EAF remains largely unknown. The study highlights the genetic heterogeneity of EAF and the limited contribution of known genes to the disorder.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2021)
Article
Genetics & Heredity
Alexandre Xavier, Rodney J. Scott, Bente Talseth-Palmer
Summary: Inherited polyposis syndromes are mainly caused by pathogenic variants in the APC gene, but a portion of FAP-like patients do not have APC gene mutations. The study found that FAP-like patients may carry pathogenic variants in genes such as MUTYH, APC, POLE, TP53, as well as inflammation-related genes, highlighting the potential role of DNA repair and inflammation-related variants in polyp development.
Article
Biotechnology & Applied Microbiology
Shilpee Pal, Gaurav Sharma, Srikrishna Subramanian
Summary: This study describes the complete genome sequence of M. rosea, conducts comparative genomic analysis to explore the putative reasons for its large genome size, and explores the potential of secondary metabolites, including the biosynthesis of polyunsaturated fatty acids.
Article
Medical Laboratory Technology
Mohammad Athar, Ibrahim S. Ghita, Amani A. Albagenny, Zainularifeen Abduljaleel, Ghulam Shadab, Ahmed Elsendiony, Saeed H. Halawani, Mohammad M. Alkazmi, Khalid Alquthami, Mohammad M. Alkhuzae, Abdulaziz A. Althebyani, Neda M. Bogari, Anas Dannoun, Faisal A. Al-Allaf
Summary: Thrombophilia is a significant cause of illness and death in certain populations, including Arabs. Next Generation Sequencing (NGS) was utilized to identify genetic variants associated with thrombophilia, uncovering known and novel variants in multiple genes. The study highlights the potential of NGS in identifying rare genetic factors predisposing individuals to thrombotic events.
CLINICA CHIMICA ACTA
(2021)
Article
Oncology
Fenfen Fu, Dongjie Zhang, Li Hu, Senthil Sundaram, Dingge Ying, Ying Zhang, Shuna Fu, Juan Zhang, Lu Yao, Ye Xu, Yuntao Xie
Summary: The study identified high-risk and moderate-risk breast cancer susceptibility genes in Chinese women, providing valuable data for genetic testing and clinical management of hereditary breast cancer in China. Patients with pathogenic variants in TP53, BRCA1, BRCA2, and PALB2 were more likely to have early onset and family history of breast cancer. Pathogenic variants of NBN, RAD50, BRIP1, and RAD51C did not show increased risk of breast cancer in Chinese women.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Obstetrics & Gynecology
M. S. Oud, B. J. Houston, L. Volozonoka, F. K. Mastrorosa, G. S. Holt, B. K. S. Alobaidi, P. F. deVries, G. Astuti, L. Ramos, R. Mclachlan, M. K. O'Bryan, J. A. Veltman, H. E. Chemes, H. Sheth
Summary: The study identified causative genetic variants in male infertility patients with severe sperm motility disorders, with high confidence in known genes in 48% of patients and novel candidate genes in 33% of patients. The results demonstrate the effectiveness of exome sequencing in diagnosing severe sperm motility disorders and revealed potential new candidate genes for further investigation.
HUMAN REPRODUCTION
(2021)
Editorial Material
Ophthalmology
Gabriel Hallali, Sjoukje E. Loudon, Anthony G. Robson, Saddek Mohand-Said, Xavier Zanlonghi, Jose-Alain Sahel, Antony T. Moore, Isabelle Audo
ACTA OPHTHALMOLOGICA
(2023)
Letter
Ophthalmology
Mridula Dilip, Zachary Koretz, Manuel A. Paez-Escamilla, Emily Hughes, Jose-Alain Sahel, Ian Conner, Marie-Helene Errera
Summary: This case report highlights a unique late complication of the Xen gel stent, namely stent-related endophthalmitis, which was preceded by flattening of the bleb. The use of B-scan and anterior chamber tap helped in the diagnosis, and intravitreal antibiotics proved effective in treating the patient.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Article
Ophthalmology
Catherine Vignal-Clermont, Patrick Yu-Wai-Man, Nancy J. Newman, Valerio Carelli, Mark L. Moster, Valerie Biousse, Prem S. Subramanian, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Alfredo A. Sadun, Thomas Klopstock, Robert C. Sergott, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Magali Taiel, Michel Roux, Jose-Alain Sahel
Summary: This study evaluated the safety profile of Lenadogene nolparvovec in patients with Leber hereditary optic neuropathy. A total of 189 patients received intravitreal injections of a recombinant adeno-associated virus 2 vector encoding the ND4 gene. The results showed that Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, and there were no serious treatment-related adverse events.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Clinical Neurology
Nancy J. Newman, Patrick Yu-Wai-Man, Prem S. Subramanian, Mark L. Moster, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Valerio Carelli, Valerie Biousse, Catherine Vignal-Clermont, Robert C. Sergott, Alfredo A. Sadun, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Fabienne Bazin, Michel Roux, Eric D. Cox, Magali Taiel, Jose-Alain Sahel
Summary: Leber hereditary optic neuropathy (LHON) is a mitochondrial blindness caused by the m.11778G>A mutation. The REFLECT phase 3 study investigated the efficacy and safety of lenadogene nolparvovec gene therapy in LHON patients. It showed improvement in visual acuity, with better results in patients who received bilateral treatment. The trial demonstrated a favorable benefit/risk profile for bilateral injections compared to unilateral injections.
Article
Genetics & Heredity
Danni Jin, Sheree A. A. Wek, Ricardo A. A. Cordova, Ronald C. C. Wek, Didier Lacombe, Vincent Michaud, Karin Musier-Forsyth
Summary: In this study, compound heterozygous variants in the EPRS1 gene were identified in a 4-year-old female patient with developmental delay, seizures, and deafness. Functional studies of the identified missense mutations confirmed significant defects in enzymatic function in vitro and contributed to the diagnosis confirmation.
Editorial Material
Medicine, Research & Experimental
Boris Rosin, Jose-Alain Sahel
Summary: Ocular and specifically retinal toxicities caused by systemic medications are common and cover various disease modalities. Established follow-up protocols are in place for many of these drugs to ensure timely detection and cessation of therapy. The recent study by Kong et al (2023) in EMBO Molecular Medicine investigated the retinal toxicity induced by deferoxamine (DFO) using both in vivo and in vitro techniques. Their findings suggest a potential protective role for alpha-ketoglutarate (AKG) supplementation against DFO toxicity.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Amrish Selvam, Sumit Randhir Singh, Supriya Arora, Manan Patel, Arnim Kuchhal, Stavan Shah, Joshua Ong, Mohammed Abdul Rasheed, Shanmukh Reddy Manne, Mohammed Nasar Ibrahim, Jose-Alain Sahel, Kiran Kumar Vupparaboina, Jay Chhablani
Summary: We conducted an automated analysis of pigment epithelial detachments (PEDs) in neovascular age related macular degeneration (nAMD) to estimate the areas of serous, neovascular, and fibrous tissues within the PEDs. By manually segmenting the PEDs and filtering the pixels using 2D kernels, we were able to classify them as serous, neovascular, or fibrous. Using specific PED composition indices, we calculated the relative areas of each tissue type within the PEDs. The accuracy of segmentation and classification was graded, and overall repeatability and reproducibility were high.
SCIENTIFIC REPORTS
(2023)
Article
Ophthalmology
Valerio Carelli, Nancy J. Newman, Patrick Yu-Wai-Man, Valerie Biousse, Mark L. Moster, Prem S. Subramanian, Catherine Vignal-Clermont, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Jean Francois Girmens, Chiara La Morgia, Adam A. DeBusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, Francois Montestruc, Michel Roux, Magali Taiel, Jose-Alain Sahel, The Lhon Study Group
Summary: Lenadogene nolparvovec is a promising gene therapy for LHON patients with MT-ND4 mutation, showing sustained visual acuity improvement compared to natural history. Incorporation of data from the latest trial REFLECT indicates that bilateral injection may offer added benefits over unilateral injection.
OPHTHALMOLOGY AND THERAPY
(2023)
Article
Ophthalmology
Jacque L. Duncan, Peiyao Cheng, Maureen G. Maguire, Allison A. Ayala, David G. Birch, Janet K. Cheetham, Todd A. Durham, Abigail T. Fahim, Carel B. Hoyng, Hiroshi Ishikawa, Michel Michaelides, Mark E. Pennesi, Jose-Alain Sahel, Katarina Stingl, Christina Y. Weng
Summary: A prospective observational study was conducted on 102 patients with USH2A-related retinal degeneration over a period of two years. It was found that quantitative measures of static perimetry significantly declined during this time. The greatest changes were observed in the full field and peripheral vision, while the central vision showed the least change.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Genetics & Heredity
Jeremy Dana, Guillaume Dorval, Christine Saint Martin, Kahina Belhous, Raphael Levy, Sandrine Marlin, Isabelle De Bie, Manon Mautret-Godefroy, Antonio Rausell, Marlene Rio, Elise Boucher-Brischoux, Tania Attie-Bitach, Nathalie Boddaert, Veronique Pingault
Summary: A retrospective cohort study was conducted to establish the genotype-phenotype correlation for CHD7-related CHARGE syndrome through unsupervised machine learning and clustering of 42 patients. Three clusters with different severities of phenotypes were identified. One patient with the most atypical phenotype and the most distal frameshift variant stood out in the third cluster. Two other patients with similar distal pathogenic variants showed tendencies towards mild and/or atypical phenotypes. These findings suggest that the milder phenotypes may result from the production of a protein retaining all functional domains, rather than escaping nonsense mediated RNA decay.
Article
Otorhinolaryngology
Malak Salame, Crystel Bonnet, Ely Cheikh Mohamed Moctar, Selma Mohamed Brahim, Abdallahi Dedy, Ledour Abdel Vetah, Fatimetou Veten, Cheikh Tijani Hamed, Christine Petit, Ahmed Houmeida
Summary: In this study, the exon 7 of the LRTOMT gene was screened in a cohort of congenital deaf children from Mauritania, and a novel pathogenic mutation was identified. The mutation was found to disrupt the structure of the encoded protein and early cochlear implant fitting seemed to improve the auditory ability of the mutation carrier. Further screening of deafness genes may reveal other variants underlying hearing impairment in the population.
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
(2023)
Article
Immunology
Sebastien Augustin, Marion Lam, Sophie Lavalette, Anna Verschueren, Frederic Blond, Valerie Forster, Lauriane Przegralek, Zhiguo He, Daniel Lewandowski, Alexis-Pierre Bemelmans, Serge Picaud, Jose-Alain Sahel, Thibaud Mathis, Michel Paques, Gilles Thuret, Xavier Guillonneau, Cecile Delarasse, Florian Sennlaub
Summary: Through studying human donor tissue, researchers have discovered that the majority of cells containing retinal melanosome/melanolipofuscin are actually melanophages, rather than migrating retinal pigment epithelial cells. They have also identified the mechanism by which melanophages form, involving the transfer of melanosomes from the retinal pigment epithelial cells to subretinal mononuclear phagocytes when the CD47 signal is blocked. These melanophages result in the formation of hyperreflective foci and are associated with RPE dysmorphia similar to intermediate AMD. Additionally, the study found that CD47 expression in human RPE decreases with age and in AMD, suggesting that boosting CD47 expression may protect RPE cells and delay AMD progression.
JOURNAL OF NEUROINFLAMMATION
(2023)
Review
Genetics & Heredity
Christine Petit, Crystel Bonnet, Saaid Safieddine
Summary: Progress in genetic studies of SNHI and multidisciplinary studies of mouse models have elucidated the molecular mechanisms underlying auditory system function, leading to the development of inner-ear gene therapy. Preclinical studies have highlighted key translational opportunities and challenges for treating monogenic forms of SNHI and associated balance disorders.
NATURE REVIEWS GENETICS
(2023)
Article
Multidisciplinary Sciences
Philippe Jean, Fabienne Wong Jun Tai, Amrit Singh-Estivalet, Andrea Lelli, Cyril Scandola, Sebastien Megharba, Sandrine Schmutz, Solene Roux, Sabrina Mechaussier, Muriel Sudres, Enguerran Mouly, Anne-Valerie Heritier, Crystel Bonnet, Adeline Mallet, Sophie Novault, Valentina Libri, Christine Petit, Nicolas Michalski
Summary: Functional molecular characterization of the cochlea has mainly been driven by the deciphering of the genetic architecture of sensorineural deafness. By analyzing the single-cell transcriptomic atlas of the mouse cochlea, researchers have identified almost all cochlear cell types and discovered three cell types, providing insights into the gene regulatory networks controlling cochlear cell differentiation and maturation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Genetics & Heredity
Godelieve Morel, Sylvain Ernest, Margaux Serey-Gaut, Laurence Jonard, Abeke Ralyath Balogoun, Marine Parodi, Natalie Loundon, Sophie Achard, Sandrine Marlin
Summary: Cochleovestibular dysfunctions are rare conditions that are often misrecognized. A study on Tunisian siblings revealed a homozygous pathogenic variation in the RIPOR2 gene, leading to congenital bilateral profound hearing and vestibular dysfunctions. However, contrary to our findings, deaf mouse and zebrafish models with Ripor2 knockout had normal vestibular function.