50,175 results match your criteria missense mutation

Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2.

Int J Biol Macromol 2021 Apr 13. Epub 2021 Apr 13.

University of Pittsburgh School of Medicine, Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address:

The current COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Read More

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Slow progression of amyotrophic lateral sclerosis in a Chinese patient carrying SOD1 p.S135T mutation.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Apr 16:1-3. Epub 2021 Apr 16.

Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China and.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Most patients die of respiratory failure within 3 years of onset. In this study, we reported a female Chinese ALS patient with SOD1 c. Read More

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Tropane-Based Ibogaine Analog Rescues Folding-Deficient Serotonin and Dopamine Transporters.

ACS Pharmacol Transl Sci 2021 Apr 28;4(2):503-516. Epub 2020 Aug 28.

Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, United States.

Missense mutations that give rise to protein misfolding are rare, but collectively, defective protein folding diseases are consequential. Folding deficiencies are amenable to pharmacological correction (pharmacochaperoning), but the underlying mechanisms remain enigmatic. Ibogaine and its active metabolite noribogaine correct folding defects in the dopamine transporter (DAT), but they rescue only a very limited number of folding-deficient DAT mutant proteins, which give rise to infantile Parkinsonism and dystonia. Read More

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Antimicrobial Resistance Profiles, Virulence Genes, and Genetic Diversity of Thermophilic Species Isolated From a Layer Poultry Farm in Korea.

Front Microbiol 2021 29;12:622275. Epub 2021 Mar 29.

Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Gangneung, South Korea.

Thermophilic species are among the major etiologies of bacterial enteritis globally. This study aimed at assessing the antimicrobial resistance (AMR) profiles, virulence genes, and genetic diversity of thermophilic species isolated from a layer poultry farm in South Korea. One hundred fifty-three chicken feces were collected from two layer poultry farms in Gangneung, South Korea. Read More

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Peters Anomaly in Nail-Patella Syndrome: A Case Report and Clinico-Genetic Correlation.

Cornea 2021 Apr 14. Epub 2021 Apr 14.

The Centre of Excellence for Rare Eye Diseases, L V Prasad Eye Institute, Hyderabad, India; The Cornea Institute, L V Prasad Eye Institute, Hyderabad, India; Jasti V Ramanamma Children's Eye Care Center, L V Prasad Eye Institute, Hyderabad, India; Kallam Anji Reddy Molecular Genetics Laboratory, Brien Holden Eye Research Centre, L V Prasad Eye Institute, Banjara Hills, Hyderabad, India; Ophthalmic Pathology Services, L V Prasad Eye Institute, Hyderabad, India; University of Illinois Eye and Ear Infirmary, Chicago, IL; and Department of Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

Purpose: The purpose of this study was to report the clinicopathological features of Peters anomaly in a child with nail-patella syndrome.

Methods: Nail-patella syndrome (NPS) is a rare autosomal dominant connective tissue disorder characterized by several anomalies of the extremities, joints and nails, glomerulopathy, and rarely ocular involvement. NPS is caused by heterozygous loss-of-functional mutations in the LMX1B gene that encodes the LIM homeodomain proteins. Read More

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A hemizygous p.R204Q mutation in the ALAS2 gene underlies X-linked sideroblastic anemia in an adult Chinese Han man.

BMC Med Genomics 2021 Apr 15;14(1):107. Epub 2021 Apr 15.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China.

Background: X-linked sideroblastic anemia (XLSA) is the most common form of congenital sideroblastic anemia (CSA), and is associated with the mutations in the 5-aminolevulinate synthase 2 (ALAS2). The genetic basis of more than 40% of CSA cases remains unknown.

Methods: A two-generation Chinese family with XLSA was studied by next-generation sequencing to identify the underlying CSA-related mutations. Read More

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[Analysis of a pedigree with inherited factor V deficiency caused by compound heterozygous mutation].

Zhonghua Xue Ye Xue Za Zhi 2021 Feb;42(2):135-139

Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.

To explore the molecular pathogenesis of a family with hereditary factor Ⅴ (FⅤ) deficiency. All the exons, flanking sequences, 5' and 3' untranslated regions of the F5 of the proband, and the corresponding mutation sites of the family members were analyzed via direct DNA sequencing. The CAT measurement was used to detect the amount of thrombin produced. Read More

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February 2021


Heart Rhythm 2021 Apr 12. Epub 2021 Apr 12.

Cardiovascular Pathology and Cardiology Units, Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Padua, Italy.

Background: Arrhythmogenic cardiomyopathy (AC) is a myocardial disease due to desmosomal mutations, whose pathogenesis remains incompletely understood.

Objective: To identify molecular pathways underlying early AC by gene expression profiling in both humans and animal models.

Methods: RNA sequencing for differentially expressed genes (DEGs) was performed on the myocardium of transgenic mice over-expressing the Desmoglein2-N271S mutation before phenotype onset. Read More

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PET/MRI Delivers Multimodal Brain Signature in Alzheimer's Disease with De Novo PSEN1 Mutation.

Curr Alzheimer Res 2021 Apr 13. Epub 2021 Apr 13.

Department of Nuclear Medicine, University of Leipzig, Leipzig. Germany.

Background: Little is known so far about the brain phenotype and the spatial interplay of different Alzheimer's disease (AD) biomarkers with structural and functional brain connectivity in the early phase of autosomal-dominant AD (ADAD). Multimodal PET/MRI might be suitable to fill this gap.

Material And Methods: We presented a 31-year-old male patient without a family history of de- mentia with progressive worsening of memory and motor function. Read More

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Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients.

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

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A Missense De Novo Variant in the CASK-interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia.

Neuropediatrics 2021 Apr 14. Epub 2021 Apr 14.

Department of Developmental Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

is a gene important for the central nervous system development-in particular for the process of neuronal migration, axonal fasciculation, and synaptogenesis-and colocalizes and cooperates in neurons with gene. Alterations of have been linked to neurodevelopmental disorders, ranging from developmental delay, to autism spectrum disorder, to attention deficit/hyperactivity disorder. The underlying mechanism is not yet fully understood, as it has been hypothesized a fully dominant effect, a risk factor role of partially penetrating variants, and a recessive inheritance pattern. Read More

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Temporal-parietal-occipital epilepsy in GEFS+ associated with SCN1A mutation.

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

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A case of juvenile CLN1- challenge in diagnosis and epilepsy treatment.

Neurocase 2021 Apr 14:1-4. Epub 2021 Apr 14.

Neurology Department, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

Classic onset of CLN1 disease is within the first year of life with developmental arrest, epilepsy and rapid progression. In an atypical variant of CLN1 disease onset is later in the juvenile epoch. Although epilepsy in the juvenile form of CLN1 often is less severe than in typical CLN1, treatment of seizures and status epilepticus may be challenging. Read More

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Multiplexing Mutation Rate Assessment: Determining Pathogenicity of Msh2 Variants in S. cerevisiae.

Genetics 2021 Apr 12. Epub 2021 Apr 12.

Genome Sciences Department, University of Washington, Seattle, WA 98195, USA.

Despite the fundamental importance of mutation rate as a driving force in evolution and disease risk, common methods to assay mutation rate are time consuming and tedious. Established methods such as fluctuation tests and mutation accumulation experiments are low-throughput and often require significant optimization to ensure accuracy. We established a new method to determine the mutation rate of many strains simultaneously by tracking mutation events in a chemostat continuous culture device and applying deep sequencing to link mutations to alleles of a DNA-repair gene. Read More

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Lack of collagen α6(IV) chain in mice does not cause severe-to-profound hearing loss or cochlear malformation, a distinct phenotype from nonsyndromic hearing loss with COL4A6 missense mutation.

PLoS One 2021 13;16(4):e0249909. Epub 2021 Apr 13.

Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Congenital hearing loss affects 1 in every 1000 births, with genetic mutations contributing to more than 50% of all cases. X-linked nonsyndromic hereditary hearing loss is associated with six loci (DFNX1-6) and five genes. Recently, the missense mutation (c. Read More

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CNGB1-related rod-cone dystrophy: a mutation review and update.

Hum Mutat 2021 Apr 12. Epub 2021 Apr 12.

Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut de la Vision, Paris, France.

CNGB1 (Cyclic nucleotide-gated channel β 1) encodes the 240-kDa β subunit of the rod photoreceptor cyclic nucleotide-gated ion channel. Disease-causing sequence variants in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). We herein present a comprehensive review and analysis of all previously reported CNGB1 sequence variants, and add 22 novel variants, thereby enlarging the spectrum to 84 variants in total, including 24 missense variants (two of which may also affect splicing), 21 nonsense, 19 splicing defects (7 at non-canonical positions), 10 small deletions, 1 small insertion, 1 small insertion-deletion, 7 small duplications and 1 gross deletion. Read More

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[Clinical features and gene mutations of 6 patients with carnitine palmitoyltransferase 1A deficiency].

Zhonghua Yi Xue Za Zhi 2021 Apr;101(14):1041-1044

Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Xinhua Children's Hospital, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.

The clinical and biochemical data and gene sequencing results of patients with carnitine palmitoyltransferase 1A deficiency were analyzed, in order to improve the understanding of the disease. Six patients (5 males and 1 female, aged from 1 to 8 years old) with carnitine palmitoyltransferase 1A deficiency from Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital between 2008 and 2019 were included. Two cases were detected by neonatal screening and had no clinical symptoms. Read More

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The lysosomal protein ABCD4 can transport vitamin B across liposomal membranes in vitro.

J Biol Chem 2021 Apr 9:100654. Epub 2021 Apr 9.

Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.

Vitamin B (cobalamin) is an essential micronutrient for human health, and mutation and dysregulation of cobalamin metabolism are associated with serious diseases, such as methylmalonic aciduria and homocystinuria. Mutations in ABCD4 or LMBRD1, which encode the ATP-binding cassette (ABC) transporter ABCD4 and lysosomal membrane protein LMBD1, respectively, lead to errors in cobalamin metabolism, with the phenotype of a failure to release cobalamin from lysosomes. However, the mechanism of transport of cobalamin across the lysosomal membrane remains unknown. Read More

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Mutation spectrum and genotype-phenotype correlations in Chinese congenital ectopia lentis patients.

Exp Eye Res 2021 Apr 9:108570. Epub 2021 Apr 9.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China. Electronic address:

Purpose: To identify the spectrum and frequency of mutations in congenital ectopia lentis (CEL) and to investigate the correlations between genotype and clinical phenotype in Chinese CEL patients.

Methods: Ninety-three participants with CEL were enrolled from March 2017 to April 2020. Ocular and systemic examinations were performed for each included patient. Read More

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Dynamic analysis of CSF1R-related leukoencephalopathy on magnetic resonance imaging: a case report.

BMC Neurol 2021 Apr 10;21(1):156. Epub 2021 Apr 10.

Department of Neurology, Liuzhou People's Hospital, Liuzhou, China.

Background: Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare and rapidly progressive leukoencephalopathy characterized by cognitive, motor, and neuropsychiatric symptoms, which is often misdiagnosed. Magnetic resonance imaging (MRI) signs and follow-up MRI of CSF1R-related leukoencephalopathy could help in establishing a diagnosis, but these features are not widely known by general neurologists.

Case Presentation: A 34-year-old man was admitted for progressive weakness of the right limbs over 8 months. Read More

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AML-Associated Mutations in DNA Methyltransferase DNMT3A.

Biochemistry (Mosc) 2021 Mar;86(3):307-318

Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia.

In mammals, DNA methylation is an essential epigenetic modification necessary for the maintenance of genome stability, regulation of gene expression, and other processes. Carcinogenesis is accompanied by multiple changes in the DNA methylation pattern and DNA methyltransferase (DNMT) genes; these changes are often associated with poor disease prognosis. Human DNA methyltransferase DNMT3A is responsible for de novo DNA methylation. Read More

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Zinc transporter mutations linked to acrodermatitis enteropathica disrupt function and cause mistrafficking.

J Biol Chem 2021 Jan 8;296:100269. Epub 2021 Jan 8.

Department of Chemistry, Michigan State University, East Lansing, Michigan, USA; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA. Electronic address:

ZIP4 is a representative member of the Zrt-/Irt-like protein (ZIP) transporter family and responsible for zinc uptake from diet. Loss-of-function mutations of human ZIP4 (hZIP4) drastically reduce zinc absorption, causing a life-threatening autosomal recessive disorder, acrodermatitis enteropathica (AE). These mutations occur not only in the conserved transmembrane zinc transport machinery, but also in the extracellular domain (ECD) of hZIP4, which is only present in a fraction of mammalian ZIPs. Read More

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January 2021

PIEZO1 mutation: a rare aetiology for fetal ascites.

BMJ Case Rep 2021 Apr 9;14(4). Epub 2021 Apr 9.

Maternal fetal Medicine, Trinity Health of New England, Hartford, Connecticut, USA.

We present a case of isolated fetal ascites diagnosed at 20 weeks' gestation. No aetiology was identified on extensive prenatal workup, including prenatal microarray. The patient terminated the pregnancy at 23 weeks' gestation. Read More

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Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns.

Exp Hematol Oncol 2021 Apr 9;10(1):27. Epub 2021 Apr 9.

Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.

Background: The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML).

Methods: We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients. Read More

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Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy - a case report.

BMC Ophthalmol 2021 Apr 9;21(1):168. Epub 2021 Apr 9.

Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Background: We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX.

Case Presentation: A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. Read More

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Clinical and genetic analysis of classical Ehlers-Danlos syndrome patient caused by synonymous mutation in COL5A2.

Mol Genet Genomic Med 2021 Apr 8:e1632. Epub 2021 Apr 8.

Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, PR China.

Background: Classical Ehlers-Danlos syndrome (cEDS) is a heterogeneous connective tissue disorder that mainly results from the germline mutation of COL5A1 and COL5A2. The majority of the COL5A2 mutations reported to date represent structural mutations, including missense or in-frame exon-skipping splice mutations. The only reported synonymous mutation was expected to affect on splicing of exon 29 by prediction programs which should be further confirmed. Read More

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Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA.

Nat Metab 2021 Apr 8. Epub 2021 Apr 8.

Computational Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Mitochondrial DNA (mtDNA) encodes protein subunits and translational machinery required for oxidative phosphorylation (OXPHOS). Using repurposed whole-exome sequencing data, in the present study we demonstrate that pathogenic mtDNA mutations arise in tumours at a rate comparable to those in the most common cancer driver genes. We identify OXPHOS complexes as critical determinants shaping somatic mtDNA mutation patterns across tumour lineages. Read More

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Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation.

Cold Spring Harb Mol Case Stud 2021 Apr 8;7(2). Epub 2021 Apr 8.

Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.

Mutations in homologous recombination (HR) genes predispose to cancer but also sensitize to chemotherapeutics. Although therapy can initially be effective, cancers frequently cease responding, leading to recurrence and poor prognosis. Here we identify a germline mutation in , a critical HR factor and known tumor suppressor, in an ovarian cancer patient with exceptionally long, progression-free survival. Read More

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De Novo mutation of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins: A case report.

Medicine (Baltimore) 2021 Apr;100(14):e25375

Department of Cardiology, Kunming Children's Hospital, Kunming, Yunnan.

Rationale: Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare congenital malformation in neonates that results in severe respiratory distress and pulmonary hypertension. ACD/MPV is caused by mutations in the FOXF1 gene. Herein, a new case of a girl with ACD/MPV carrying a novel pathogenic variant of FOXF1 was reported. Read More

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