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Biochem Biophys Res Commun 2021 Apr 12;557:20-25. Epub 2021 Apr 12.

State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, National Pesticide Engineering Research Center (Tianjin), Nankai University, 94 Weijin Road, Tianjin, 300071, China. Electronic address:

Protoporphyrinogen IX oxidase (PPO) is the last common enzyme in chlorophyll and heme biosynthesis pathways. In human, point mutations on PPO are responsible for the dominantly inherited disorder disease, Variegate Porphyria (VP). Of the VP-causing mutation site, the Arg59 is by far the most prevalent VP mutation residue identified. Read More

Cortex 2021 Mar 19;139:99-115. Epub 2021 Mar 19.

Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA.

Although executive dysfunction is the characteristic cognitive marker of behavioral variant frontotemporal dementia (bvFTD), episodic memory deficits are relatively common, and may be present even during the prodromal disease phase. In a cohort of mutation carriers with mild behavioral and/or cognitive symptoms consistent with prodromal bvFTD, we aimed to investigate patterns of performance on an abbreviated list learning task, with a particular focus on recognition memory. We further aimed to characterize the cognitive prodromes associated with the three major genetic causes of frontotemporal dementia, as emerging evidence suggests there may be subtle differences in cognitive profiles among carriers of different genetic mutations. Read More

Am Fam Physician 2021 Apr;103(8):481-492

Gundersen Medical Foundation Family Medicine Residency, La Crosse, WI, USA.

Hypermobile Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders are the most common symptomatic joint hypermobility conditions seen in clinical practice. The 2017 International Classification of the Ehlers-Danlos syndromes replaced previous terms for symptomatic joint hypermobility with hypermobile EDS and introduced the term hypermobility spectrum disorders for patients not meeting diagnostic criteria for hypermobile EDS. Both are diagnosed by applying the 2017 diagnostic criteria, which also excludes other less common conditions presenting with joint hypermobility such as other forms of EDS and heritable connective tissue disorders. Read More

Hum Mol Genet 2021 Apr 15. Epub 2021 Apr 15.

Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

Progressive degeneration of retinal ganglion cells (RGCs) is a major characteristic of glaucoma, whose underlying mechanisms are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal tension glaucoma (NTG), directly affecting RGCs without high intraocular pressure and causing severe glaucomatous symptoms in clinical settings. A systematic analysis of the NTG mouse model is crucial for better understanding of the underlying pathological mechanisms for glaucoma. Read More

J Clin Immunol 2021 Apr 14. Epub 2021 Apr 14.

Rady Children's Hospital San Diego, San Diego, CA, USA.

Purpose: IKAROS, encoded by IKZF1, is a member of the IKAROS family of zinc-finger transcription factors playing critical roles in lymphocyte development, differentiation, and tumor suppression. Several studies demonstrated that IKZF1 mutations affecting DNA binding or homo-/hetero-dimerization are mostly associated with common variable immunodeficiency, combined immunodeficiency, or hematologic manifestations. Herein we report a likely de novo, nonsense IKZF1 mutation (p. Read More

Neurol Sci 2021 Apr 15. Epub 2021 Apr 15.

Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Alzheimer's disease (AD) can be either sporadic or familial, and familial forms of AD accounts for only 5% of the cases. So far, autosomal dominantly inherited mutations in "Presenilin 1" (PSEN1), "Presenilin 2" (PSEN2), and "Amyloid precursor protein" (APP) genes were associated with familial AD. Amid the others, pathogenic mutations in the PSEN2 gene are less common. Read More

Brain 2021 Apr 15. Epub 2021 Apr 15.

Department of Morphology, Surgery and Experimental Medicine, St. Anna Hospital, University of Ferrara, Ferrara, 44124, Italy.

Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. Read More

iScience 2021 Apr 13;24(4):102306. Epub 2021 Mar 13.

Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York NY, USA.

RASopathies represent a family of mostly autosomal dominant diseases that are caused by missense variants in the rat sarcoma viral oncogene/mitogen activated protein kinase (RAS/MAPK) pathway including KRAS, NRAS, BRAF, RAF1, and SHP2. These variants are associated with overlapping but distinct phenotypes that affect the heart, craniofacial, skeletal, lymphatic, and nervous systems. Here, we report an analysis of 13 Drosophila transgenic lines, each expressing a different human RASopathy isoform. Read More

Bio Protoc 2021 Mar 20;11(6):e3954. Epub 2021 Mar 20.

Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, Sigmaringen, Germany.

7,8-dihydro-8-oxoguanine (8-oxoG) is one of the most common and mutagenic oxidative DNA damages induced by reactive oxygen species (ROS). Since ROS is mainly produced in the inner membranes of the mitochondria, these organelles and especially the mitochondrial DNA (mtDNA) contained therein are particularly affected by this damage. Insufficient elimination of 8-oxoG can lead to mutations and thus to severe mitochondrial dysfunctions. Read More

J Hepatocell Carcinoma 2021 6;8:211-222. Epub 2021 Apr 6.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.

Purpose: The effects of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC), in the progression of liver cancer are unknown. In this study, we attempted to clarify the clinical significance and mechanism of PIGC in hepatocellular carcinoma (HCC).

Patients And Methods: To explore the expression profiles, DNA methylation, mutation status, clinical relevance, and prognostic value of PIGC in patients with HCC, a series of bioinformatic databases and websites were searched. Read More

J Cancer 2021 5;12(9):2498-2506. Epub 2021 Mar 5.

Department of Pathology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

The stage T1 urothelial bladder cancer (T1 UBC) tumor grade classification is important for prognosis and clinical management. However, the reproducibility of this two-grade classification system is limited in regards to pathological diagnosis, and there is lack of ideal, objective and easily detected markers for pathological diagnosis. In our study, bladder urothelial lesions from a total of 124 patients diagnosed pathologically after transurethral resection of the bladder tumor (TURBT) were collected, including non-cancerous lesions from 33 patients and lesions from 91 T1 UBC patients. Read More

Cancer Manag Res 2021 8;13:3081-3100. Epub 2021 Apr 8.

Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.

Ovarian cancer is a common and complex malignancy with poor prognostic outcome. Most women with ovarian cancer are diagnosed with advanced stage disease due to a lack of effective detection strategies in the early stage. Traditional treatment with cytoreductive surgery and platinum-based combination chemotherapy has not significantly improved prognosis and 5-year survival rates are still extremely poor. Read More

Cancer Manag Res 2021 7;13:3055-3065. Epub 2021 Apr 7.

Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Guangzhou, Guangdong, People's Republic of China.

Purpose: This study aimed to investigate AKT gene mutation status in Chinese breast cancer patients.

Methods: The study included 411 breast cancer patients hospitalized in Guangdong Provincial People's Hospital (GDPH) from June 1, 2017 to September 27, 2018. Mastectomy or breast conserving surgery was performed, and tissue samples were subjected to next-generation sequencing (NGS) to determine AKT gene mutation status. Read More

Sci Rep 2021 Apr 14;11(1):8154. Epub 2021 Apr 14.

Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Read More

J Virol 2021 Apr 14. Epub 2021 Apr 14.

Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium

Human adenoviruses (HAdVs) are a large family of DNA viruses counting more than 100 genotypes divided into seven species (A-G) and inducing respiratory tract infections, gastroenteritis and conjunctivitis. Genetically modified adenoviruses are also used as vaccines, gene therapies and anti-cancer treatments. The APOBEC3s are a family of cytidine deaminases that restrict viruses by introducing mutations in their genomes. Read More

Acta Neuropathol Commun 2021 Apr 14;9(1):69. Epub 2021 Apr 14.

Department of Neurosurgery, Rutgers-Robert Wood Johnson Medical School & University Hospital, Rutgers-New Jersey Medical School, New Brunswick, NJ, 08901, USA.

Prognostic molecular subgrouping of glioblastoma is an ongoing effort and the current classification includes IDH-wild-type and IDH-mutant entities, the latter showing significantly better prognosis. We performed a comparative integrated analysis of the FGFR glioblastoma subgroup consisting of 5 cases from a prospective 101-patient-cohort. FGFR alterations included FGFR2-TACC2 and FGFR2 amplifications arising in a multifocal IDH-mutant glioblastoma with unexpected 2. Read More

Genome Med 2021 Apr 14;13(1):59. Epub 2021 Apr 14.

Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, Antwerp, Belgium.

Knowledge of the molecular etiology of neurodegenerative brain diseases (NBD) has substantially increased over the past three decades. Early genetic studies of NBD families identified rare and highly penetrant deleterious mutations in causal genes that segregate with disease. Large genome-wide association studies uncovered common genetic variants that influenced disease risk. Read More

Nucleosides Nucleotides Nucleic Acids 2021 Apr 14:1-11. Epub 2021 Apr 14.

Medical Genomics Research Center, Islamic Azad Tehran Medical Sciences University, Tehran, Iran.

Type 2 diabetes mellitus (T2DM) is a multifactorial polygenic disease. Potassium inwardly-rectifying channel, subfamily J, member 11 ( gene mutations can result in susceptibility of T2DM. The aim of this study is to investigate the relationship between risk of T2DM and its complications (retinopathy & renal) and polymorphisms rs5210 and rs5215 of the gene in a group of Iranian population. Read More

Epileptic Disord 2021 Apr 12. Epub 2021 Apr 12.

Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Napoli, Italy.

Most families with genetic epilepsy with febrile seizures plus show a mutation in the sodium channel alpha 1 subunit gene, however, but there is much phenotypic heterogeneity and focal epilepsy remains relatively rare. Here, we report a family with electroclinical features indicative of temporal-parietal-occipital carrefour epilepsy with common occurrence of post-ictal migraine. We studied a four-generation family including nine affected subjects by means of EEG and MRI. Read More

Indian J Pathol Microbiol 2021 Apr-Jun;64(2):390-393

Department of Paediatric Urology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India.

Gonadal dysgenesis is a distinct variety of Disorders of Sexual Differentiation (DSD) characterised by incomplete or defective formation of the gonads due to either structural or numerical anomalies of the sex chromosomes or mutations in the genes involved in the development of the gland. Here we present two such rare cases that presented during childhood. Both patients presented with ambiguous genitalia with a 45XO/46XY mosaic chromosome pattern. Read More

Ann Hematol 2021 Apr 13. Epub 2021 Apr 13.

Internal Medicine and Hematology, Mustafa Kemal University Faculty of Medicine, Hatay, Turkey.

Thalassemia is a common genetic disorder. We aimed to present thalassemia mutation data that covers a period of 7 years from the Mediterranean region of Turkey by comparing with hemoglobin indices and to contribute to prenatal diagnosis and genetic counseling studies which should be decided very quickly. In this study, in which a retrospective archive was scanned, the cases were first grouped as α and β thalassemia, and then β thalassemia mutations were examined in a total of 5 groups as UTR-Pro, Codon, IVS, β, and β. Read More

Ann Transl Med 2021 Mar;9(6):500

Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China.

Background: Hepatocellular carcinoma (HCC) often has an insidious onset and rapid progression. Often, when the disease is first diagnosed, the opportune time for surgical intervention has already lapsed. In addition, the effects of systemic treatment is relatively unsatisfactory. Read More

Transl Androl Urol 2021 Mar;10(3):1486-1498

Andrology and IVF Laboratory, Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.

Male infertility is a common and complex disease, manifesting as a wide range of phenotypes, ranging from apparently normal semen parameters with an inexplicable inability to conceive, to the complete absence of sperm production. The diversity of male infertility phenotypes, coupled with the extreme complexity of spermatogenesis has significantly confounded the identification of the underlying genetic causes for these conditions, though incremental progress has been made, particularly in the past decade. In this review, we discuss the progress that has been made to date, tools and resources that have proven effective in accelerating discovery of novel genetic markers for male infertility, and areas in which we see the greatest potential for advancing the field in the coming years. Read More

Transl Androl Urol 2021 Mar;10(3):1391-1400

Division of Urology, Department of Surgery, Mount Sinai Hospital and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.

Cystic fibrosis (CF) is a rare autosomal-recessive disorder manifested as multisystem organ dysfunction. The cystic fibrosis transmembrane conductance regulator (CFTR) protein functions as an ion transporter on the epithelium of exocrine glands, regulating secretion viscosity. The gene, encoded on chromosome 7, is required for the production and trafficking of the intact and functional CFTR protein. Read More

Plant Biotechnol (Tokyo) 2020 Dec;37(4):397-403

Department of Biomaterial Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

The study of Carbohydrate-Active enZymes (CAZymes) associated with plant cell wall metabolism is important for elucidating the developmental mechanisms of plants and also for the utilization of plants as a biomass resource. The use of recombinant proteins is common in this context, but heterologous expression of plant proteins is particularly difficult, in part because the presence of many cysteine residues promotes denaturation, aggregation and/or protein misfolding. In this study, we evaluated two phenotypes of methylotrophic yeast as expression hosts for expansin from peach ( (L. Read More

Nat Commun 2021 04 13;12(1):2224. Epub 2021 Apr 13.

BioMarin Pharmaceutical Inc., Novato, CA, USA.

Prioritizing genes for translation to therapeutics for common diseases has been challenging. Here, we propose an approach to identify drug targets with high probability of success by focusing on genes with both gain of function (GoF) and loss of function (LoF) mutations associated with opposing effects on phenotype (Bidirectional Effect Selected Targets, BEST). We find 98 BEST genes for a variety of indications. Read More

Mol Cancer Ther 2021 Apr 13. Epub 2021 Apr 13.

Vivace Therapeutics.

Mutations in the neurofibromatosis type 2 (NF2) gene that limit or abrogate expression of functional Merlin are common in malignant mesothelioma. Merlin activates the Hippo pathway to suppress nuclear translocation of YAP and TAZ, the major effectors of the pathway that associate with the TEAD transcription factors in the nucleus and promote expression of genes involved in cell proliferation and survival. Here we described the discovery of compounds that selectively inhibit YAP/TAZ-TEAD promoted gene transcription, block TEAD auto-palmitoylation, and disrupt interaction between YAP/TAZ and TEAD. Read More

Clin Cancer Res 2021 Apr 13. Epub 2021 Apr 13.

LTG, NIH/NCI/DCEG.

Purpose: Exome and whole-genome sequencing of muscle-invasive bladder cancer (BC) has revealed important insights into the molecular landscape; however, there are few studies of non-muscle invasive BC with detailed risk factor information.

Experimental Design: We examined the relationship between smoking and other BC risk factors and somatic mutations and mutational signatures in bladder tumors. Targeted sequencing of frequently mutated genes in BC was conducted in 322 formalin-fixed paraffin-embedded bladder tumors from a population-based case-control study. Read More

Tumori 2021 Apr 13:3008916211009303. Epub 2021 Apr 13.

Medical Oncology Department, Bakırköy Sadi Konuk Training and Research Hospital, Istanbul, Turkey.

Introduction: Lung cancer is the most common cause of cancer-related death in the world. Changes in the treatment of metastatic lung cancer in recent years have made targetable mutations gain importance. teration is one of these driver mutations and crizotinib is a tyrosine kinase inhibitor used in therapy. Read More

Praxis (Bern 1994) 2021 Apr;110(5):249-250

Institut für Klinische Chemie, Universitätsspital Zürich.

CME Laboratory 63/Answers: Diagnostics of Iron Metabolism Abstract: Iron deficiency is common and affects the course of many chronic diseases. The diagnosis of absolute and manifest iron deficiency anemia can be easily made by measuring hemoglobin and serum ferritin levels. In inflammatory diseases, the diagnosis can be facilitated by additional laboratory parameters such as soluble transferrin receptor. Read More