Article
Multidisciplinary Sciences
Malte Zorn, Jirko Kuehnisch, Sebastian Bachmann, Wenke Seifert
Summary: This study investigated the pathogenic effect of missense variants in the VPS13B gene on Cohen syndrome through clinical patient information, in silico predictions, and in vitro testing. The study found that 6 out of 10 missense variants were likely pathogenic, providing insights into the pathomechanisms of Cohen syndrome.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Alka Malhotra, Alban Ziegler, Li Shu, Renee Perrier, Louise Amlie-Wolf, Elizabeth Wohler, Nara Lygia de Macena Sobreira, Estelle Colin, Adeline Vanderver, Omar Sherbini, Katrien Stouffs, Emmanuel Scalais, Alessandro Serretti, Magalie Barth, Benjamin Navet, Paul Rollier, Hui Xi, Hua Wang, Hainan Zhang, Denise L. Perry, Alessandra Ferrarini, Roberto Colombo, Alexander Pepler, Adele Schneider, Kiyotaka Tomiwa, Nobuhiko Okamoto, Naomichi Matsumoto, Noriko Miyake, Ryan Taft, Xiao Mao, Dominique Bonneau
Summary: Rare de novo variants in LMBRD2 were identified in 10 individuals with developmental delay, intellectual disability, thin corpus callosum, microcephaly and seizures. These findings suggest that these variants may cause a previously unrecognized early-onset neurodevelopmental disorder.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Genetics & Heredity
Nicholas Borja, Paulo Borjas-Mendoza, Stephanie Bivona, LeShon Peart, Joanna Gonzalez, Brittney Keira Johnson, Shengru Guo, Roman Yusupov, Guney Bademci, Mustafa Tekin
Summary: Recently, recurrent de novo missense variants in H4 histone genes have been associated with a novel neurodevelopmental syndrome characterized by intellectual disability, developmental delay, and other variable findings. This report presents a case of a 4-year-old male with autism and developmental delay who was suspected to have Angelman syndrome but tested negative. Genome sequencing identified a H4 histone gene variant that met criteria for likely pathogenic classification and confirmed to be de novo. Comparison of the findings with previous cases supports the delineation of a neurodevelopmental syndrome caused by these missense H4 gene variants.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Ignacio Arroyo Carrera, Miguel Fernandez-Burriel, Pablo Lapunzina, Jair Antonio Tenorio, Veronica Deyanira Garcia Navas, Elena Marquez Isidro
Summary: Missense and frameshift pathogenic variants, as well as microdeletions involving the TBL1XR1 gene, have been linked to intellectual disability, autism, Rett-like features, and schizophrenia in patients. This case report describes a novel missense variant in the TBL1XR1 gene associated with overlapping features of Pierpont syndrome and autism, expanding the phenotypic spectrum of pathogenic variants in this gene.
Article
Genetics & Heredity
Ilaria Parenti, Daphne Lehalle, Caroline Nava, Erin Torti, Elsa Leitao, Richard Person, Takeshi Mizuguchi, Naomichi Matsumoto, Mitsuhiro Kato, Kazuyuki Nakamura, Stella A. de Man, Heidi Cope, Vandana Shashi, Undiagnosed Diseases Network, Jennifer Friedman, Pascal Joset, Katharina Steindl, Anita Rauch, Irena Muffels, Peter M. van Hasselt, Florence Petit, Thomas Smol, Gwenael Le Guyader, Frederic Bilan, Arthur Sorlin, Antonio Vitobello, Christophe Philippe, Ingrid M. B. H. van de Laar, Marjon A. van Slegtenhorst, Philippe M. Campeau, Ping Yee Billie Au, Mitsuko Nakashima, Hirotomo Saitsu, Tatsuya Yamamoto, Yumiko Nomura, Raymond J. Louie, Michael J. Lyons, Amy Dobson, Astrid S. Plomp, M. Mahdi Motazacker, Frank J. Kaiser, Andrew T. Timberlake, Sabine A. Fuchs, Christel Depienne, Cyril Mignot
Summary: The CHD5 gene, located in the critical 1p36 microdeletion region, encodes a subunit of the NuRD complex required for neuronal development. Variants in this gene were identified in 16 unrelated individuals, showing features like intellectual disability, speech delay, and epilepsy.
Article
Genetics & Heredity
Mederic Jeanne, Helene Demory, Aubin Moutal, Marie-Laure Vuillaume, Sophie Blesson, Rose-Anne Thepault, Sylviane Marouillat, Judith Halewa, Saskia M. Maas, M. Mahdi Motazacker, Grazia M. S. Mancini, Marjon A. van Slegtenhorst, Avgi Andreou, Helene Cox, Julie Vogt, Jason Laufman, Natella Kostandyan, Davit Babikyan, Miroslava Hancarova, Sarka Bendova, Zdenek Sedlacek, Kimberly A. Aldinger, Elliott H. Sherr, Emanuela Argilli, Eleina M. England, Severine Audebert-Bellanger, Dominique Bonneau, Estelle Colin, Anne-Sophie Denomme-Pichon, Brigitte Gilbert-Dussardier, Bertrand Isidor, Sebastien Kury, Sylvie Odent, Richard Redon, Rajesh Khanna, William B. Dobyns, Stephane Bezieau, Jerome Honnorat, Bernhard Lohkamp, Annick Toutain, Frederic Laumonnier
Summary: The CRMP family proteins, including CRMP5/DPYSL5, play important roles in neurodevelopment, with mutations leading to brain malformations and intellectual disabilities. These mutations affect the interaction of DPYSL5 with neuronal cytoskeleton-associated proteins, influencing dendritic outgrowth.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Pediatrics
Liqing Wang, Jianwei Li, Qiuhong Xiong, Yong-An Zhou, Ping Li, Changxin Wu
Summary: This study reports the first discovery of a DKC1 gene mutation in a Chinese family, which is associated with the phenotype of mucocutaneous triad. The findings broaden the understanding of disease variation, genotype-phenotype correlations, and facilitate clinical diagnosis of DC in China.
FRONTIERS IN PEDIATRICS
(2022)
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
Genetics & Heredity
Luisa Averdunk, Heinrich Sticht, Harald Surowy, Hermann-Josef Luedecke, Margarete Koch-Hogrebe, Hessa S. Alsaif, Kimia Kahrizi, Hamad Alzaidan, Bashayer S. Alawam, Mohamed Tohary, Cornelia Kraus, Sabine Endele, Erin Wadman, Julie D. Kaplan, Stephanie Efthymiou, Hossein Najmabadi, Andre Reis, Fowzan S. Alkuraya, Dagmar Wieczorek
Summary: The missense variant p.(Arg367Trp) in YARS1 causes a distinct multisystem disorder affecting a non-canonical domain with cytokine-like functions. Phenotypic heterogeneity associates with the different affected YARS1 domains, and impaired protein translation is likely not the exclusive mechanism of ARS1-associated disorders.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Chemistry, Multidisciplinary
Mark Agostino, Fiona McKenzie, Chloe Buck, Karen J. Woodward, Vanessa J. Atkinson, Dimitar N. Azmanov, Julian Ik-Tsen Heng
Summary: Missense variants in UBE3A can cause neurodevelopmental conditions. This study reports a novel missense variant in UBE3A and investigates its impact on protein function using molecular simulations.
Article
Cell Biology
Yeming Yang, Xiao Li, Jieping Wang, Junkai Tan, Bernie Fitzmaurice, Patsy M. Nishina, Kuanxiang Sun, Wanli Tian, Wenjing Liu, Xuyang Liu, Bo Chang, Xianjun Zhu
Summary: This study reports a new mouse model of early-onset glaucoma caused by a mutation in the PITX2 gene, which leads to increased intraocular pressure and progressive death of retinal ganglion cells. The model exhibits features similar to human glaucoma pathologies and indicates elevated oxidative stress in the inner retina. Treatment with N-Acetyl-L-cysteine shows a significant neuroprotective effect on glaucoma-associated neuropathies.
CELL DEATH & DISEASE
(2021)
Article
Biodiversity Conservation
Changqiao Hong, Xiaobin Jin
Summary: This study developed a green index (GI) to evaluate green levels in China's CBAs and found that the green levels were higher in South China and lower in North China. From 2001 to 2018, the average green level in China's CBAs experienced a V-shaped change with improvements in most regions post turning point. Regional differences in green levels decreased, and city-level differences contributed significantly more to the total difference in China compared to provincial and regional levels. More attention should be focused on greenery in CBAs at the city level to implement sustainable urban development and land management policies in the future.
ECOLOGICAL INDICATORS
(2021)
Article
Genetics & Heredity
Eri Imagawa, Latisha Moreta, Vinod K. Misra, Claire Newman, Tsuyoshi Konuma, Kimihiko Oishi
Summary: A mild phenotype including cleft palate, hypotonia, developmental delay, and minor dysmorphisms was observed in a 3-year-old male with a missense RBM10 variant. The variant affected the expression of downstream genes NUMB and TNRC6A through alternative splicing regulation, resulting in non-lethal developmental delays.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Melita Kaltak, Zelia Corradi, Rob W. J. Collin, Jim Swildens, Frans P. M. Cremers
Summary: This study investigated the impact of synonymous and missense variants in ABCA4 on pre-mRNA splicing. It identified 16 out of 18 analyzed variants that caused splice aberrations. These findings highlight the causal role of coding ABCA4 variants in splicing abnormalities, improving the severity assessment of missense and synonymous ABCA4 variants, and guiding new treatment strategies for STGD1.
HUMAN MOLECULAR GENETICS
(2023)
Review
Neurosciences
Osama Hamadelseed, Mike K. S. Chan, Michelle B. F. Wong, Thomas Skutella
Summary: This study critically reviews the unique changes in brain structure and cognitive function in Down syndrome and compares them with other neurodevelopmental disorders. The findings suggest specific neuroanatomic and histopathological features in Down syndrome, deficits in language and memory, and differences from related syndromes. Individuals with Down syndrome show both impairments and preserved abilities in various cognitive, linguistic, and social domains.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biology
Zuhier Awan, Nuha Alrayes, Zeenath Khan, Majid Almansouri, Abdul Ibrahim Hussain Bima, Haifa Almukadi, Hussam Ibrahim Kutbi, Preetha Jayasheela Shetty, Noor Ahmad Shaik, Babajan Banaganapalli
Summary: This study identified potential genetic biomarkers for familial hypercholesterolemia (FH) by studying the global gene expression profile of blood cells. Dysregulated expression of genes related to lipid homeostasis, immune responses, and cell adhesion molecules was found in FH patients. The involvement of dysregulated thyroid hormone and ErbB signaling pathways, as well as the enrichment of specific genes, were observed. The key hub genes JAK3, PLCG2, and ZEB2 were identified to contribute to inflammation and immune response related phenotypes. These findings provide insights into the immune dysregulation underlying atherosclerosis among FH patients and may contribute to the development of genomic medicine for cardiovascular diseases.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Genetics & Heredity
Nirmal Vadgama, Alexander Kreymerman, Jackie Campbell, Olga Shamardina, Christiane Brugger, Genomics England Research Consortium, Alexandra M. Deaconescu, Richard T. Lee, Christopher J. Penkett, Casey A. Gifford, Mark Mercola, Jamal Nasir, Ioannis Karakikes
Summary: COVID-19 susceptibility and progression are closely correlated with age, gender, ethnicity, and pre-existing health conditions. Host genetics, including variants in the ACE2 receptor, may play a role in determining COVID-19 risk and could partially account for differences in disease susceptibility among ethnic groups.
FRONTIERS IN GENETICS
(2022)
Article
Pediatrics
Huda Husain Al-Numan, Rana Mohammed Jan, Najla bint Saud Al-Saud, Omran M. Rashidi, Nuha Mohammad Alrayes, Hadeel A. Alsufyani, Abdulrahman Mujalli, Noor Ahmad Shaik, Mahmoud Hisham Mosli, Ramu Elango, Omar I. Saadah, Babajan Banaganapalli
Summary: This study identified the molecular basis of early onset inflammatory bowel disease (IBD) in Arab patients through whole exome sequencing. The ITGAV and FN1 genes were found to be associated with IBD, with abundant expression in the gastrointestinal tract and immune organs. The dysregulation of these genes disrupts immune homeostasis and may induce intestinal inflammation. These findings provide new insights into the molecular etiology of pediatric onset IBD.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Atta Ullah Khan, Ibrar Khan, Muhammad Ismail Khan, Muhammad Latif, Muhammad Imran Siddiqui, Shafi Ullah Khan, Thet Thet Htar, Ghazala Wahid, Ikram Ullah, Fehmida Bibi, Asifullah Khan, Muhammad Imran Naseer, Go Hun Seo, Musharraf Jelani
Summary: In this study, a consanguineous Pakistani family was investigated, and novel compound heterozygous variants in the GFM1 gene were identified in four affected siblings. These variants may lead to mitochondrial translation defects and severe phenotypes, but the affected siblings survived without life-threatening conditions at the ages of 10-17 years.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Multidisciplinary Sciences
Elbatool G. G. Elalem, Musharraf Jelani, Alaa Khedr, Aftab Ahmad, Tareef Y. Y. Alaama, Mohamed Nabeel Alaama, Huda M. M. Al-Kreathy, Zoheir A. A. Damanhouri
Summary: This study investigated the association between CYP3A4 and CYP3A5 gene single nucleotide polymorphisms (SNPs) and the response to simvastatin treatment in hypercholesterolemia patients. The results showed that CYP3A4 and CYP3A5 gene mutations were associated with the patients' response to statins.
Article
Genetics & Heredity
Nuha Alrayes, Bayan A. Mallah, Noha M. Issa, Babajan Banaganapalli, Noor Ahmad Shaik, Khalidah K. Nasser, Bandar Ali Alshehri, Zahurul A. Bhuiyan, Amnah Y. Bdier, Jumana Y. Al-Aama
Summary: The study identified a novel heterozygous de novo mutation in the LRP1 gene in TOF patients in Saudi Arabia. This mutation was predicted to be pathogenic and affects the structure and function of the protein. Functional biology data from knock out mouse models confirmed the association of this gene mutation with cardiac defects and lethality. The findings contribute to accurate diagnosis and understanding of the molecular mechanisms and pathophysiology of TOF.
Article
Genetics & Heredity
Qaiser Zaman, Muhammad Abbas Khan, Kalsoom Sahar, Gauhar Rehman, Hamza Khan, Mehwish Rehman, Najumuddin, Ilyas Ahmad, Muhmmad Tariq, Osama Yousef Muthaffar, Angham Abdulrhman Abdulkareem, Fehmida Bibi, Muhammad Imran Naseer, Muhammad Shah Faisal, Naveed Wasif, Musharraf Jelani
Summary: This study reported rare cases of MPV17, SACS, PRX, and GJB1 gene mutations causing Charcot-Marie-Tooth disease and spastic ataxia of Charlevoix-Saguenay type in the Pakistani population. Whole exome sequencing was found to be a useful tool in diagnosing complex multigenic and phenotypically overlapping genetic disorders such as CMT and ARSACS.
Article
Genetics & Heredity
Qaiser Zaman, Sadeeda, Muhammad Anas, Gauhar Rehman, Qadeem Khan, Aiman Iftikhar, Mashal Ahmad, Muhammad Owais, Ilyas Ahmad, Osama Yousef Muthaffar, Angham Abdulrhman Abdulkareem, Fehmida Bibi, Musharraf Jelani, Muhammad Imran Naseer
Summary: Two consanguineous Pakhtun families with Hermansky-Pudlak syndrome (HSP) were studied, and novel variants in HSP3 and HSP4 genes were identified. The identified variants expand the pathogenic spectrum of HPS3 and HPS4 genes and provide molecular diagnostics for genetic counseling and reducing the disease burden in future generations.
Article
Biotechnology & Applied Microbiology
Qaiser Zaman, Aiman Iftikhar, Gauhar Rehman, Qadeem Khan, Amin Najumuddin, Amin Jan, Jamshid Khan, Muhammad Anas, Osama Yousef Liba, Muhammad Umair, Osama Yousef Muthaffar, Angham Abdulrhman Abdulkareem, Fehmida Bibi, Muhammad Imran Naseer, Musharraf Jelani
Summary: This study reports for the first time the variations in ATP6V0A2 and ALDH18A1 genes in the Pakhtun ethnicity of Pakistani population. It confirms that whole-exome sequencing can be used as a first-line diagnostic test for patients with cutis laxa, and provides a basis for population screening and premarital testing to reduce the burden of the disease in future generations.
JOURNAL OF GENE MEDICINE
(2023)
Article
Genetics & Heredity
Abu Bakar, Sulaiman Shams, Nousheen Bibi, Asmat Ullah, Wasim Ahmad, Musharraf Jelani, Osama Yousef Muthaffar, Angham Abdulrhman Abdulkareem, Turki S. S. Abujamel, Absarul Haque, Muhammad Imran Naseer, Bushra Khan
Summary: This study identified a pathogenic gene variant causing Dyggve-Melchior-Clausen Syndrome in the Pakistani population. The findings of this study are important for prenatal screening, genetic counseling, and carrier testing in the Pakistani community.
Article
Genetics & Heredity
Angham Abdulrhman Abdulkareem, Qaiser Zaman, Hamza Khan, Sabar Khan, Gauhar Rehman, Nabeel Tariq, Mashal Ahmad, Muhammad Owais, Osama Yousef Najumuddin, Osama Yousef Muthaffar, Fehmida Bibi, Rin Khang, Seung Woo Ryu, Muhammad Imran Naseer, Musharraf Jelani
Summary: This study identified four novel variants in CARS2, ARSA, CNTN2 and CLCN4 genes associated with epilepsy in five Pakistani families. These variants were found to be pathogenic and molecular diagnosis was successfully achieved through whole exome sequencing and Sanger sequencing. This study suggests that exome sequencing should be performed as a first-line molecular diagnostic test in familial cases.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Murad Ali Rahat, Fazal Akbar, Akhtar Rasool, Muhammad Ilyas, Allah Rakha, Sulaiman Shams, Musharraf Jelani, Fehmida Bibi, Bader H. Shirah, Angham Abdulrhman Abdulkareem, Muhammad Imran Naseer, Muhammad Israr
Summary: The study aimed to validate the IrisPlex system and determine the prevalence of eye color in the Pakhtoon population in the Malakand Division. The results showed that brown eye color was the most common among the local population. This study may have implications for future population genetics and forensic research.
Article
Clinical Neurology
Mona M. Almramhi, Chris Finan, Catherine S. Storm, Amand F. Schmidt, Demis A. Kia, Rachel Coneys, Sandesh Chopade, Aroon D. Hingorani, Nick W. Wood
Summary: The study suggests that RAC2 is a genetic modifier of MS risk and supports a causal effect of HDL-C on MS risk.
Article
Genetics & Heredity
Nuha Alrayes, Noha M. Issa, Omar Y. Alghubayshi, Jumana Y. Al-Amaa, Ashwaq Hassan Alsabban, Dalal Sameer Al Shaer, Reem Abdullah Alyoubi, Khalidah K. Nasser, Yaser M. Alkhiary
Summary: This study aims to explore the association between the quality of life (QoL) in children with Down syndrome (DS) and its relationship with demographic characteristics of both parents and children. The study found that the QoL of children with DS showed high scores in the psychological well-being, autonomy, parental relations, school, and learning environment domains. However, the physical and social well-being and peer domains had lower scores, although still considered good scores. Family income had a positively significant influence on all QoL domains. Parental age was found to influence psychological well-being, while parental education and the relationship between the parent and child influenced social well-being. Lastly, the child's gender was found to have an impact on the school and learning environment domain.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Genetics & Heredity
Nirmal Vadgama, Mohamed Ameen, Laksshman Sundaram, Sadhana Gaddam, Casey Gifford, Jamal Nasir, Ioannis Karakikes
Summary: This study provides important insights into the genetic etiology of cardiomyopathies, highlighting the contribution of variants in noncoding regulatory regions and oligogenic inheritance mechanisms. The findings suggest that a combination of prioritized variants and genetic modifiers play a role in the development of cardiomyopathies. Additionally, rare noncoding variants in regulatory elements of known cardiomyopathy genes were found to be associated with the disease, uncovering potential targets for future investigations.