Review
Genetics & Heredity
Yadong Fu, Yueyun Zhou, Qing'e Zhang, Jingjing Dong, Jianli Zheng, Min Li, Jianbing Liu
Summary: This study reports the phenotype and pathogenic gene analysis results of a mild case of Cenani-Lenz syndrome in a Chinese patient. Exome sequencing technology identified a novel missense variant in the LRP4 gene associated with this condition.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Genetics & Heredity
Dhanya Yesodharan, Vivek Krishnan, Indu R. Nair, Aparna Ganapathy, Ashraf U. Mannan, Sheela Nampoothiri
Summary: Cenani Lenz syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the LRP4 gene, leading to limb malformations and dysmorphism. The severity of the disease varies depending on the type of genetic variant.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Biochemistry & Molecular Biology
Yu-Wen Cheng, Chia-Tung Wu, Chi-Jen Chang, Yung-Hsin Yeh, Gwo-Jyh Chang, Hsin-Yi Tsai, Lung-An Hsu
Summary: Through whole-exome sequencing, we identified a novel AGCGACAC deletion (S981fs) in the hERG gene of an LQT2 patient. Functional expression of the mutant K channel was restored by lowering temperature and using potassium channel inhibitors or openers. Our study reveals the mechanisms underlying LQT2 and offers potential therapeutic avenues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pediatrics
Shuolin Li, Jing Liu, Yuan Yuan, Aizhen Lu, Fang Liu, Li Sun, Quanli Shen, Libo Wang
Summary: This study reports a rare case of Kabuki syndrome with pneumorrhagia, expanding the phenotypic spectrum of the syndrome. The patient carried a novel missense variant in the KMT2D gene and experienced recurrent pulmonary hemorrhage during treatment.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Ya Liu, Meihua Tan, Luhang Cai, Lihui Lv, Qingqing Chen, Wei Chen, Hang Yang, Yaping Xu
Summary: In this study, whole-exome sequencing was used to investigate the genetic causes of severe-profound hearing loss in Chinese Han children. Several novel genes and variants associated with hearing loss were identified, expanding our understanding of the heterogeneity of hereditary hearing loss.
Article
Genetics & Heredity
Hao Wang, Guanjun Luo, Wensheng Hu, Jin Mei, Yue Shen, Min Wang, Yuan Tan, Yang Yang, Chao Lu, Yong Zhao, Ming Qi
Summary: This study identified new mutations associated with Joubert syndrome (JS) in the ARMC9 gene, expanding the mutation spectrum. The findings suggest that ARMC9 may play a role in the pathogenesis of JS by affecting the development of primary cilia.
FRONTIERS IN GENETICS
(2022)
Article
Cell Biology
Yong Guo, Jing Jin, Zhenni Zhou, Yihui Chen, Li Sun, Chunwu Zhang, Xiaoru Xia
Summary: This study identified a rare CPT2 mutation in a large Chinese pedigree with gout. Functional studies revealed that the mutant protein induces protein degradation and affects the binding ability of CPT2 to UCP2. This study provides novel insight into the genetic etiology of gout.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Genetics & Heredity
Hammal Khan, Angie En Qi Chong, Muhammad Bilal, Shoaib Nawaz, Abdullah, Sanaullah Abbasi, Amir Hussain, Shabir Hussain, Imran Ullah, Hamid Ali, Shifeng Xue, Wasim Ahmad
Summary: Cenani-Lenz syndrome (CLS) is a rare autosomal-recessive congenital disorder affecting distal limb development, characterized by syndactyly and/or oligodactyly. Mutations in the LRP4 gene on human chromosome 11p11.2-q13.1 cause CLS, leading to inhibition of bone formation and Wnt signaling. The study identified novel homozygous missense variants in the LRP4 gene in Pakistani families with CLS, affecting the functionality of LRP4.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Oncology
Lucas W. Thornblade, Paul Wong, Daneng Li, Susanne G. Warner, Sue Chang, Mustafa Raoof, Jonathan Kessler, Arya Amini, James Lin, Vincent Chung, Gagandeep Singh, Yuman Fong, Laleh G. Melstrom
Summary: Cholangiocarcinomas are rare cancers with potentially targetable mutations, and a third of patients undergoing resection in the past decade have had tumor genomic profiling, with 89% harboring targetable mutations. While targeted therapies were identified in most sequenced tumors, only 4% of patients received these therapies, highlighting the potential for precision medicine in the future care of cholangiocarcinoma.
Article
Genetics & Heredity
Hammal Khan, Glenn Koh, Angie En Qi Chong, Muhammad Zahid, Shabir Hussain, Hamid Ali, Wasim Ahmad, Shifeng Xue
Summary: In this study, a novel variant was identified in a family with isolated syndactyly using exome sequencing. Functional studies suggest that this variant in AFF3 may cause a loss-of-function phenotype distinct from previously characterized AFF3 variants.
Article
Genetics & Heredity
Zekiye Altun, Hongling Yuan, Burcin Baran, Safiye Aktas, Esra Esmeray Sonmez, Can Kucuk, Nur Olgun
Summary: This study aimed to investigate genetic aberrations in neuroblastoma (NB) by comparing high and low-risk NB patients using whole-exome sequencing (WES) and to reveal the heterogeneity and association between somatic variants and clinical features. Seven NB patients with clinical data were included (4 in the low-risk group and 3 in the high-risk group). Somatic variants associated with NB genes were identified and analyzed using bioinformatics methods. Several gene variations were found in both groups, including oncogenes and tumor suppressor genes. Candidate gene variations were associated with chromatin remodeling complexes, the RAS pathway, cell proliferation, and DNA repair mechanism. Some variations were specific to high-risk patients or low-risk patients. Comparisons with the cBioportal cancer genomic database identified common gene variants in high-risk patients but not in low-risk patients. GO/KEGG enrichment analysis was performed to explore relevant biological processes and molecular pathways related to gene variants, which can help unravel the molecular mechanisms of NB tumorigenesis and the phenotypic differences between high-risk and low-risk patients.
Article
Immunology
Wanru Guo, Xuewen Feng, Ming Hu, Yanwan Shangguan, Jiafeng Xia, Wenjuan Hu, Xiaomeng Li, Zunjing Zhang, Yunzhen Shi, Kaijin Xu
Summary: The study found that the use of whole exome sequencing in patients with FUO can improve genetic diagnosis and treatment. In this study, positive results were found in 7 out of 15 sequenced samples, involving eight different genes.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Heetae Park, Kazuyoshi Hosomichi, Yong-Il Kim, Atsushi Tajima, Tetsutaro Yamaguchi
Summary: This study used whole-exome sequencing (WES) to investigate the genetic background of dental abnormality called dens evaginatus (DE). The study identified gene variants of TLR3 and MDC1 as etiologic factors for DE. The findings contribute to understanding the etiology of DE and can potentially improve treatment and preventive measures, as well as aid in the development of regenerative medicine and gene therapy strategies.
APPLIED SCIENCES-BASEL
(2022)
Article
Genetics & Heredity
Pedro Guimaraes de Azevedo, Maria de Lourdes Rabelo Guimaraes, Anna Luiza Braga Albuquerque, Rayane Benfica Alves, Bianca Gomes Fernandes, Flavia Marques de Melo, Raony Guimaraes Correa Do Carmo Lisboa Cardenas, Eitan Friedman, Luiz De Marco, Luciana Bastos-Rodrigues
Summary: This study investigated the genetic variants in two Brazilian families with obstructive sleep apnea syndrome (OSAS) that followed a seemingly autosomal dominant inheritance pattern. Whole exome sequencing identified variants in COX20, PTPDC1, and TMOD4 genes as strong candidate genes associated with OSAS phenotype in these families. Further studies are needed to confirm the contribution of these variants in a larger and more diverse population of OSAS cases.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Xiaofang Shen, Shun Zhang, Xin Zhang, Taifeng Zhou, Yongjun Rui
Summary: This study identified two variants in the GLI3 gene that are associated with polydactyly and syndactyly, leading to truncation and degradation of the GLI3 protein and affecting SHH signaling.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Correction
Genetics & Heredity
Ai Ling Koh, Carine Bonnard, Nur Ain Binte Ali, Bruno Reversade, Saumya Jamuar
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Emmanuelle Szenker-Ravi, Tim Ott, Muznah Khatoo, Anne Moreau de Bellaing, Wei Xuan Goh, Yan Ling Chong, Anja Beckers, Darshini Kannesan, Guillaume Louvel, Priyanka Anujan, Vydianathan Ravi, Carine Bonnard, Sebastien Moutton, Patric Schoen, Melanie Fradin, Estelle Colin, Andre Megarbane, Linda Daou, Ghassan Chehab, Sylvie Di Filippo, Caroline Rooryck, Jean-Francois Deleuze, Anne Boland, Nicolas Arribard, Rukiye Eker, Sumanty Tohari, Alvin Yu-Jin Ng, Marlene Rio, Chun Teck Lim, Birgit Eisenhaber, Frank Eisenhaber, Byrappa Venkatesh, Jeanne Amiel, Hugues Roest Crollius, Christopher T. Gordon, Achim Gossler, Sudipto Roy, Tania Attie-Bitach, Martin Blum, Patrice Bouvagnet, Bruno Reversade
Summary: Phylogenomic and genetic analyses have identified an ancestral module of genes expressed specifically in ciliated left-right organizer tissue, which is essential for left-right axis specification in humans and certain vertebrates. CIROP, a newly discovered gene encoding an extracellular protein, is shown to be specifically expressed in ciliated LROs and plays a crucial role in distinguishing left from right in vertebrates. Mutations in the CIROP gene have been found in human patients with recessive situs anomalies, highlighting the importance of this gene in determining left-right asymmetry.
Article
Cell & Tissue Engineering
Robin Canac, Amandine Caillaud, Bastien Cimarosti, Aurore Girardeau, Hanan Hamamy, Bruno Reversade, Carine Bonnard, Zeina R. Al Sayed, Laurent David, Jeremie Poschmann, Patricia Lemarchand, Guillaume Lamirault, Nathalie Gaborit
Summary: Animal studies have demonstrated the significant role of Irx5 in cardiac development and its regulation of ventricular electrical repolarization gradient in the adult heart. Mutations in IRX5 have also been linked to cardiac conduction defects in humans. To further understand the function of IRX5 in cardiac development and cardiomyocyte function, researchers have generated three genetically-modified human induced pluripotent stem cell lines.
STEM CELL RESEARCH
(2022)
Article
Genetics & Heredity
Abigail Y. T. Loh, Sanja Spoljar, Granville Y. W. Neo, Nathalie Escande-Beillard, Marc Leushacke, Monique N. H. Luijten, Byrappa Venkatesh, Carine Bonnard, Maurice A. M. van Steensel, Henning Hamm, Andrew Carmichael, Neil Rajan, Thomas J. Carney, Bruno Reversade
Summary: Huriez syndrome is a rare genetic skin disorder characterized by scleroatrophic hands and feet, hypoplastic nails, palmoplantar keratoderma, and a predisposition to cutaneous squamous cell carcinoma. This study reported three HRZ families from different regions and identified germline SMARCAD1 pathogenic variants. The findings suggest that Huriez syndrome may be allelic to Adermatoglyphia and Basan syndrome, sharing similar genetic and phenotypic features.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
D. Hettiarachchi, S. M. Subasinghe, G. G. Anandagoda, Hetalkumar Panchal, P. S. Lai, V. H. W. Dissanayake
Summary: We report a novel frameshift variant in the PCNT gene and describe a previously unreported phenotype for Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II.
BMC MEDICAL GENOMICS
(2022)
Article
Clinical Neurology
Amin Ziaei, Marta Garcia-Miralles, Carola Radulescu, Harwin Sidik, Aymeric Silvin, Han-Gyu Bae, Carine Bonnard, Nur Amirah Binte Mohammad Yusof, Costanza Ferrari Bardile, Liang Juin Tan, Alvin Yu Jin Ng, Sumanty Tohari, Leila Dehghani, Lily Henry, Xin Yi Yeo, Sejin Lee, Byrappa Venkatesh, Sarah R. Langley, Vahid Shaygannejad, Bruno Reversade, Sangyong Jung, Florent Ginhoux, Mahmoud A. Pouladi
Summary: Ermin is essential for maintaining myelin integrity and normal saltatory conduction. Its deficiency causes de-compacted and fragmented myelin sheaths, slower conduction, and progressive neurological deficits. Ermin deficiency also leads to inflammatory activation and increased susceptibility to immune-mediated demyelination insult. These findings provide insights into the development of inflammatory white matter disorders and myelin stability-targeted therapies.
Correction
Genetics & Heredity
Emmanuelle Szenker-Ravi, Tim Ott, Muznah Khatoo, Anne Moreau de Bellaing, Wei Xuan Goh, Yan Ling Chong, Anja Beckers, Darshini Kannesan, Guillaume Louvel, Priyanka Anujan, Vydianathan Ravi, Carine Bonnard, Sebastien Moutton, Patric Schoen, Melanie Fradin, Estelle Colin, Andre Megarbane, Linda Daou, Ghassan Chehab, Sylvie Di Filippo, Caroline Rooryck, Jean-Francois Deleuze, Anne Boland, Nicolas Arribard, Rukiye Eker, Sumanty Tohari, Alvin Yu-Jin Ng, Marlene Rio, Chun Teck Lim, Birgit Eisenhaber, Frank Eisenhaber, Byrappa Venkatesh, Jeanne Amiel, Hugues Roest Crollius, Christopher T. Gordon, Achim Gossler, Sudipto Roy, Tania Attie-Bitach, Martin Blum, Patrice Bouvagnet, Bruno Reversade
Article
Multidisciplinary Sciences
Claribel Tian Yu Foo, Yi Hui To, Astrid Irwanto, Alvin Yu-Jin Ng, Benedict Yan, Sophia Tsong Huey Chew, Jianjun Liu, Lian Kah Ti
Summary: This study describes the variant landscape of the RYR1 gene in Singapore, identifying pathogenic and likely pathogenic variants that are mainly missense mutations and occur at higher frequencies in Asians than globally. These findings will facilitate genetic screening for RYR1-related conditions.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Chik Hong Kuick, Jia Ying Tan, Deborah Jasmine, Tohari Sumanty, Alvin Y. J. Ng, Byrrappa Venkatesh, Huiyi Chen, Eva Loh, Sudhanshi Jain, Wan Yi Seow, Eileen H. Q. Ng, Derrick W. Q. Lian, Shui Yen Soh, Kenneth T. E. Chang, Zhi Xiong Chen, Amos H. P. Loh
Summary: Our study found that mutations in chromosome 1 genes are common in 1p-intact neuroblastoma, but may not always disrupt the function of authentic 1p tumor suppressors. These findings suggest a complex interplay of 1p gene aberrations contributing to tumor suppressor inactivation in neuroblastoma.
Article
Multidisciplinary Sciences
Shifeng Xue, Thanh Thao Nguyen Ly, Raunak S. Vijayakar, Jingyi Chen, Joel Ng, Ajay S. Mathuru, Frederique Magdinier, Bruno Reversade
Summary: This study reveals that Smchd1 regulates Hox gene expression at an epigenetic level in mammals, and its loss causes precocious and ectopic Hox transcription. The loss of maternal Smchd1 also leads to Hox epimutations and affects the vertebral patterning in offspring. Furthermore, the regulation is mediated by the direct interacting partner Lrif1.
NATURE COMMUNICATIONS
(2022)
Article
Developmental Biology
Hyuk Nam Kwon, Kristen Kurtzeborn, Vladislav Iaroshenko, Xing Jin, Abigail Loh, Nathalie Escande-Beillard, Bruno Reversade, Sunghyouk Park, Satu Kuure
Summary: Nephron endowment plays a crucial role in adult renal health, and defects in the molecular regulation of nephron progenitors can lead to reduced nephron mass. This study characterized the metabolic consequences of MAPK/ERK deficiency and identified pyruvate and proline as important factors in nephron progenitor maintenance.
Article
Dermatology
Mingfeng Li, Kenneth Lay, Andreas Zimmer, Kristin Technau-Hafsi, Jasmine Wong, Antonia Reimer-Taschenbrecker, Jan Rohr, Ebtesam Abdalla, Judith Fischer, Bruno Reversade, Cristina Has
Summary: A previously unreported NLRP1 gene variant was identified, leading to different clinical presentations in two sisters. The variant triggered the activation of inflammation and resulted in different severity of skin manifestations.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Nasrinsadat Nabavizadeh, Annkatrin Bressin, Mohammad Shboul, Ricardo Moreno Traspas, Poh Hui Chia, Carine Bonnard, Emmanuelle Szenker-Ravi, Burak Saribas, Emmanuel Beillard, Umut Altunoglu, Zohreh Hojati, Scott Drutman, Susanne Freier, Mohammad El-Khateeb, Rajaa Fathallah, Jean-Laurent Casanova, Wesam Soror, Alaa Arafat, Nathalie Escande-Beillard, Andreas Mayer, Bruno Reversade
Summary: Exome sequencing has revolutionized the identification of germline variations responsible for Mendelian diseases, but it cannot capture non-coding regions. This study demonstrates how RNA-seq can complement exome sequencing by identifying a deep intronic mutation in a gene associated with Osteogenesis Imperfecta and neonatal progeria syndrome. The mutation alters pre-mRNA processing and leads to exon skipping, revealing the importance of transcriptomic approaches in understanding the molecular mechanisms of human diseases.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biology
Eva Hasel de Carvalho, Shivani S. Dharmadhikari, Kateryna Shkarina, Jingwei Rachel Xiong, Bruno Reversade, Petr Broz, Maria Leptin
Summary: The researchers constructed a light-responsive form of the inflammasome adaptor protein, allowing tight control of inflammasome formation within cells. By introducing this construct into zebrafish, they were able to induce inflammasome formation in individual skin cells. They found that the resulting cell death from inflammasome formation varied morphologically in different cell types.
