Article
Obstetrics & Gynecology
Tingting Zou, Qingsong Xi, Zhenxing Liu, Zhou Li, Meiqi Hou, Lixia Zhu, Lei Jin, Xianqin Zhang
Summary: In this study, a novel mutation in the ZP1 gene was identified using whole-exome sequencing. The study confirmed the important role of the ZP1 gene in human female reproduction, expanded the mutation spectrum of the gene, and increased its application in the clinical and molecular diagnosis of EFS.
REPRODUCTIVE SCIENCES
(2022)
Article
Cell Biology
Lihong Tan, Minghui Yu, Yaxin Li, Shanshan Xue, Jing Chen, Yihui Zhai, Xiaoyan Fang, Jialu Liu, Jiaojiao Liu, Xiaohui Wu, Hong Xu, Qian Shen
Summary: Congenital anomalies of the kidney and urinary tract (CAKUT) is a common birth defect caused by complex genetic and environmental factors. Recent studies have suggested the involvement of long non-coding RNAs in the development of the kidney and urinary tract system. Research using PB transposon-based mutagenesis found that abnormal expression of Rik may lead to a reduction in UB branches by downregulating Bmp4, contributing to the development of CAKUT.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Christian H. Burns, Belinda Yau, Anjelica Rodriguez, Jenna Triplett, Drew Maslar, You Sun An, Reini E. N. van der Welle, Ross G. Kossina, Max R. Fisher, Gregory W. Strout, Peter O. Bayguinov, Tineke Veenendaal, David Chitayat, James A. J. Fitzpatrick, Judith Klumperman, Melkam A. Kebede, Cedric S. Asensio
Summary: VPS41 is essential for insulin granule biogenesis and regulated insulin secretion. Loss of VPS41 results in reduced insulin granule number, changes in transmembrane protein composition, and defects in granule-regulated exocytosis, ultimately leading to diabetes in mice.
Article
Genetics & Heredity
Minna Luo, Zaisheng Lin, Tian Zhu, Minjun Jin, Dan Meng, Ruida He, Zongfu Cao, Yue Shen, Chao Lu, Ruikun Cai, Yong Zhao, Xueyan Wang, Hui Li, Shijing Wu, Xuan Zou, Guanjun Luo, Li Cao, Min Huang, Huike Jiao, Huafang Gao, Ruifang Sui, Chengtian Zhao, Xu Ma, Muqing Cao
Summary: The study identified IFT74 as a gene associated with JBTS, and revealed pathological effects including attenuated ciliogenesis, altered distribution of IFT proteins and ciliary membrane proteins, and disrupted hedgehog signaling in patients with specific variants.
GENETICS IN MEDICINE
(2021)
Article
Andrology
Muhammad Zubair, Ranjha Khan, Ao Ma, Uzma Hameed, Mazhar Khan, Tanveer Abbas, Riaz Ahmad, Jian-Teng Zhou, Wasim Shah, Ansar Hussain, Nisar Ahmed, Ihsan Khan, Khalid Khan, Yuan-Wei Zhang, Huan Zhang, Li-Min Wu, Qing-Hua Shi
Summary: Mutations in the CCDC103 gene may be a cause of severe sperm qualitative defects, which can affect male fertility.
ASIAN JOURNAL OF ANDROLOGY
(2022)
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)
Review
Clinical Neurology
Srinivasarao Repudi, Daniel J. Steinberg, Nimrod Elazar, Vanessa L. Breton, Mark S. Aquilino, Afifa Saleem, Sara Abu-Swai, Anna Vainshtein, Yael Eshed-Eisenbach, Bharath Vijayaragavan, Oded Behar, Jacob J. Hanna, Elior Peles, Peter L. Carlen, Rami Aqeilan
Summary: WWOX-related epileptic encephalopathy (WOREE) syndrome is a neurodevelopmental disorder caused by bi-allelic mutations in the WWOX gene, leading to symptoms such as intractable epilepsy and developmental delay. Studies in mice and human brain organoids have shown evidence of myelination defects and hyperexcitability associated with WWOX function.
Article
Genetics & Heredity
Mojiang Li, Yingshu Li, Huixing Liu, Haiyan Zhou, Wanqin Xie, Qinghua Peng
Summary: This study describes a patient with a homozygous ADAMTSL2 p.Gly656Ser variant, further increasing our understanding of the genotype-phenotype correlation in acromelic dysplasias.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Yufeng Wang, Qingtao Qin, Yang Yang, Shan Dong, Yuting Liu, Molin Wang, Yongxin Zou, Yaoqin Gong, Haibin Zhou, Baichun Jiang
Summary: We identified a novel pathogenic variant in BTG4 in a female patient with primary infertility and recurrent failure of in vitro fertilization with zygotic cleavage failure. Functional investigation showed the importance of the C-terminal of BTG4. Our findings indicate BTG4 as a potential diagnostic and therapeutic target for patients suffering from zygotic cleavage failure.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2023)
Article
Genetics & Heredity
Jessica L. Haigh, Anna Adhikari, Nycole A. Copping, Tyler Stradleigh, A. Ayanna Wade, Rinaldo Catta-Preta, Linda Su-Feher, Iva Zdilar, Sarah Morse, Timothy A. Fenton, Anh Nguyen, Diana Quintero, Samrawit Agezew, Michael Sramek, Ellie J. Kreun, Jasmine Carter, Andrea Gompers, Jason T. Lambert, Cesar P. Canales, Len A. Pennacchio, Axel Visel, Diane E. Dickel, Jill L. Silverman, Alex S. Nord
Summary: In this study, we focused on the functional role of a potentially redundant Scn1a promoter and found that deletion of the non-coding 1b regulatory region led to severe reductions in the expression of Scn1a and Na(V)1.1 throughout the brain, resulting in seizures and behavioral deficits. This work highlights the importance of non-canonical and seemingly redundant promoters in the regulation of a major epilepsy risk gene, SCN1A.
Article
Genetics & Heredity
Dina Marek-Yagel, Shachar Abudi-Sinreich, Michal Macarov, Alvit Veber, Nechama Shalva, Amit Mary Philosoph, Ben Pode-Shakked, May Christine V. Malicdan, Yair Anikster
Summary: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism (OCA) and bleeding diathesis. This study reports a novel HPS3 deletion mutation in six affected individuals of Ashkenazi Jewish descent, suggesting that the prevalence of HPS-3 in this population is more common than previously thought.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Mengmeng Lu, Shuai Kong, Mingfei Xiang, Yu Wang, Jingjing Zhang, Zongliu Duan, Xiaomin Zha, Fengsong Wang, Yunxia Cao, Fuxi Zhu
Summary: In this study, a novel homozygous missense mutation of PMFBP1 was identified in an infertile male from a consanguineous family, leading to a significant decrease in expression of the mutant protein in sperm. This mutation may be a cause of acephalic spermatozoa syndrome, providing a basis for genetic counseling for the patient.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2021)
Article
Genetics & Heredity
Laura De Rosa, Dominga Fasano, Lucrezia Zerillo, Valeria Valente, Antonella Izzo, Nunzia Mollo, Giuseppina Amodio, Elena Polishchuk, Roman Polishchuk, Mariarosa Anna Beatrice Melone, Chiara Criscuolo, Anna Conti, Lucio Nitsch, Paolo Remondelli, Giovanna Maria Pierantoni, Simona Paladino
Summary: This study demonstrates that the structure and dynamics of early endosomes are altered in cells from individuals with Down syndrome (DS). Recycling trafficking is also compromised in these cells. Furthermore, the study suggests that alterations in the endolysosomal pathway are already present early in development. Overexpression of the lipid phosphatase synaptojanin 1 (Synj1) recapitulates the alterations observed in DS cells, supporting a role for this enzyme in the pathogenesis of DS.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Yeonmi Lee, Taeho Kim, Miju Lee, Seongjun So, Mustafa Zafer Karagozlu, Go Hun Seo, In Hee Choi, Peter C. W. Lee, Chong-Jai Kim, Eunju Kang, Beom Hee Lee
Summary: The research focused on a patient diagnosed with Pearson syndrome, whose father had a POLG gene mutation and mother had a SSBP1 gene mutation, resulting in large mtDNA deletions. The study results suggest that the co-deficient expression of POLG and SSBP1 genes could contribute to the development of mtDNA deletion.
Article
Endocrinology & Metabolism
Huan Chen, Ali Wu, Mark L. Zeidel, Weiqun Yu
Summary: This study found that disrupted smooth muscle insulin receptor-mediated signaling in diabetic bladder dysfunction caused myogenic abnormalities, leading to voiding dysfunction.
Article
Cell Biology
Giuliana C. Coatti, Alekh Paranjapye, Ann Harris
Summary: Primary human epididymis epithelial (HEE) cells are valuable reagents for functional studies on the human epididymis. Previous research has found that a cocktail of small molecules can extend the replicative potential and maintain the differentiation status of HEE cells. This study is important for understanding the molecular, cellular, and functional aspects of the epididymis.
CELL AND TISSUE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Larissa Costa de Almeida, Felipe Antunes Calil, Natalia Cestari Moreno, Paula Rezende-Teixeira, Luiz Alberto Beraldo de Moraes, Paula Christine Jimenez, Carlos Frederico Martins Menck, Joao Agostinho Machado-Neto, Leticia Veras Costa-Lotufo
Summary: DNA-targeting agents have clinical significance in anticancer chemotherapy, but their widespread use is limited due to toxicity. This study used in silico modeling and transcriptomics to characterize the DNA repair pathways activated by pradimicin-IRD treatment. Pradimicin-IRD was found to be a DNA intercalating agent and can potentially inhibit DNA-binding proteins. Genes related to DNA repair functions were modulated by pradimicin-IRD, providing insights for further research on this compound as a new antineoplastic agent.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Genetics & Heredity
Reza Maroofian, Stephanie Efthymiou, Mohnish Suri, Fatima Rahman, Maha S. Zaki, Shazia Maqbool, Najwa Anwa, Victor L. Ruiz-Perez, Shira Yanovsky-Dagan, Orly Elpeleg, Sniya Sudhakar, Kshitij Mankad, Tamar Harel, Henry Houlden
Summary: In this study, biallelic loss-of-function and missense MAPKAPK5 variants were identified in three unrelated individuals from consanguineous families. These patients exhibited a syndromic neurodevelopmental disorder characterized by severe global developmental delay, intellectual disability, characteristic facial morphology, brachycephaly, digital anomalies, hair and nail defects, neuroradiological findings, and other features. This study consolidates the causality of loss of MAPKAPK5 function and further delineates the molecular and phenotypic spectrum associated with this new ultra-rare neurodevelopmental syndrome.
JOURNAL OF MEDICAL GENETICS
(2023)
Letter
Clinical Neurology
Anderson Rodrigues Brandao de Paiva, Andre Luiz Santos Pessoa, Paulo Ribeiro Nobrega, Cristiane Araujo Martins Moreno, David S. Lynch, Lucas Mitsuo Taniguti, Joao Paulo Kitajima, Fernando Freua, Bruno Della-Ripa, Paulina Cunha, Isabella Peixoto de Barcelos, Lucia Ines Macedo-Souza, Carlos Augusto Takeuchi, Antonio Milton Silva Garcia, Flavia Nardes, Ramiro Fontao, Sergio Antonio Antoniuk, Monica Troncoso, Norma Specola, Consuelo Durand, Bianca de Aguiar Coelho Silva Madeiro, Maria Juliana Rodovalho Doriqui, Diane Vergara, Henry Houlden, Fernando Kok
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Dermatology
Lilian Kelly Faria Licariao Rocha, Paula Ferreira, Marcelo A. Gianotti, Joao Avancini, Carlos F. M. Menck, Ligia P. Castro, Zilda Najjar Prado de Oliveira, Maria C. Rivitti, Luciana P. Samorano, Naiura Vieira Pereira, Cyro Festa Neto
AUSTRALASIAN JOURNAL OF DERMATOLOGY
(2023)
Article
Oncology
Camila Corradi, Juliana B. Vilar, Vanessa C. Buzatto, Tiago A. de Souza, Ligia P. Castro, Veridiana Munford, Rodrigo De Vecchi, Pedro A. F. Galante, Fernanda Orpinelli, Thiago L. A. Miller, Jose L. Buzzo, Mirian N. Sotto, Paulo Saldiva, Jocelanio W. de Oliveira, Sulamita C. W. Chaibub, Alain Sarasin, Carlos F. M. Menck
Summary: This manuscript discusses the genetic alterations, including mutation signatures and retrotransposition insertions, found in the skin tumors of XP-V patients deficient in translesion synthesis (TLS). These alterations provide mechanistic insights into the functions of DNA polymerase eta. The study also highlights the importance of warning XP-V patients about the risks associated with sunlight exposure and tobacco usage, as well as the potential for using checkpoint blockade immunotherapy in these patients.
Article
Genetics & Heredity
Maha S. S. Zaki, Wessam E. E. Sharaf-Eldin, Karima Rafat, Hasnaa M. M. Elbendary, Mona Kamel, Nour Elkhateeb, Mahmoud M. M. Noureldeen, Mohamed A. A. Abdeltawab, Abdelrahim A. A. Sadek, Mona L. L. Essawi, Tracy Lau, David Murphy, Mohamed S. S. Abdel-Hamid, Henry Holuden, Mahmoud Y. Y. Issa, Joseph G. G. Gleeson
Summary: This study reports on 46 patients from 23 unrelated Egyptian families with ALS2-related disorders. The patients did not show any signs of lower motor neuron involvement. The study identified various disease-causing ALS2 variants and found a correlation between disease severity and age at onset. The study expands the mutational spectrum of the ALS2 gene and suggests that IAHSP and JPLS are part of one entity without phenotype-genotype correlation.
Article
Biochemistry & Molecular Biology
Tomas J. Steeman, Andrea M. J. Weiner, Aldana P. David, Andres Binolfi, Nora B. Calcaterra, Pablo Armas
Summary: RNA guanine quadruplexes (G4s) formed within precursors of microRNAs (pre-miRNAs) regulate miRNA biogenesis during zebrafish embryogenesis. The G4 formed in the precursor of miRNA 150 (pre-miR-150) acts as a conserved regulatory structure competing with the stem-loop structure necessary for miRNA biogenesis, leading to knock-down phenotypes associated with the target gene myb. Inhibition of G4 formation and stabilization using a G4 ligand rescues the phenotypes related to myb knock-down.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Joseph Magrino, Veridiana Munford, Davi Jardim Martins, Thais K. Homma, Brendan Page, Christl Gaubitz, Bruna L. Freire, Antonio M. Lerario, Juliana Brandstetter Vilar, Antonio Amorin, Emilia K. E. Leao, Fernand Kok, Carlos F. M. Menck, Alexander A. L. Jorge, Brian A. Kelch
Summary: PCNA is a crucial protein involved in DNA replication and maintenance. Two variants, S228I and C148S, have been identified to cause a rare DNA repair disorder called PARD. While S228I affects protein interactions, C148S does not change the structure or affinity of PCNA. However, both variants exhibit a thermostability defect. This study advances our understanding of PARD and highlights the importance of PCNA levels in the disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Andrey A. Yurchenko, Fatemeh Rajabi, Tirzah Braz-Petta, Hiva Fassihi, Alan Lehmann, Chikako Nishigori, Jinxin Wang, Ismael Padioleau, Konstantin Gunbin, Leonardo Panunzi, Fanny Morice-Picard, Pierre Laplante, Caroline Robert, Patricia L. Kannouche, Carlos F. M. Menck, Alain Sarasin, Sergey I. Nikolaev
Summary: Xeroderma pigmentosum (XP) is a rare genetic disorder associated with an increased risk of skin cancer. In this study, the authors analyze skin cancer genomes from five different XP groups, revealing genetic and molecular factors related to the mutational profile and UV-induced mutagenesis in XP.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
M. Makenzie Beaman, Lucia Guidugli, Monia Hammer, Chelsea Barrows, Anne Gregor, Sangmoon Lee, Kristen L. Deak, Marie T. McDonald, Courtney Jensen, Maha S. Zaki, Amira T. Masri, Charlotte A. Hobbs, Joseph G. Gleeson, Jennifer L. Cohen
Summary: We report six individuals from three unrelated families with oculogastrointestinal neurodevelopmental syndrome and Dandy-Walker malformation caused by biallelic CAPN15 variants. Our findings confirm previous reports and also establish a new association between Dandy-Walker malformation and CAPN15-related disease. Mouse model data support the important role of CAPN15 protein in normal cerebellar development.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Mahmoud Y. Issa, Mona A. Hafez, Samir M. Mounir, Sherif F. Abdel Ghafar, Maha S. Zaki, Mohamed S. Abdel-Hamid
Summary: PEHO and PEHO-like syndromes are rare infantile disorders characterized by intellectual disabilities, hypotonia, convulsions, optic atrophy, and progressive brain atrophy. This study describes a new family from Egypt with a lethal epileptic encephalopathy caused by a homozygous frameshift variant in the CCDC88A gene.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Mohamed S. Abdel-Hamid, Ghada M. H. Abdel-Salam, Sherif F. Abdel-Ghafar, Maha S. Zaki
Summary: Pathogenic variants in the PNPLA8 gene have been linked to congenital microcephaly, early onset epileptic encephalopathy, neurodegeneration, and cerebellar ataxia. This study identified two new variants in PNPLA8 in three patients, expanding the understanding of the disease phenotype. The findings suggest that the location of the variant, rather than its type, is strongly associated with the onset of the disease.
Article
Biochemistry & Molecular Biology
Davi Jardim Martins, Jenny Kaur Singh, Tiya Jahjah, Alexandre Teixeira Vessoni, Giovana da Silva Leandro, Matheus Molina Silva, Denis Serge Francois Biard, Annabel Quinet, Carlos Frederico Martins Menck
Summary: Xeroderma pigmentosum (XP) variant cells deficient in Polη polymerase show increased sensitivity to UV radiation, affecting cell proliferation and migration. Polι may act as a backup for Polη in bypassing UV-induced photoproducts.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Amanda Faria Assoni, Thiago Giove Mitsugi, Rene Wardenaar, Raiane Oliveira Ferreira, Elisa Helena Farias Jandrey, Gabriela Machado Novaes, Isabela Fonseca de Oliveira Granha, Petra Bakker, Carolini Kaid, Mayana Zatz, Floris Foijer, Oswaldo Keith Okamoto
Summary: This study found that high expression of VAPB in medulloblastoma is associated with decreased patient survival, and VAPB is required for normal proliferation of medulloblastoma cells.
SCIENTIFIC REPORTS
(2023)