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Gene mutation

Anastasia K Atabekova, Anna V Pankratenko, Svetlana S Makarova, Ekaterina A Lazareva, Robert A Owens, Andrey G Solovyev, Sergey Y Morozov
Human B-cell receptor-associated protein BAP31 (HsBAP31) is the endoplasmic reticulum-resident protein involved in protein sorting and transport as well as pro-apoptotic signaling. Plant orthologs of HsBAP31 termed 'plant BAP-like proteins' (PBL proteins) have thus far remained unstudied. Recently, the PBL protein from Nicotiana tabacum (NtPBL) was identified as an interactor of Nt-4/1, a plant protein known to interact with plant virus movement proteins and affect the long-distance transport of potato spindle tuber viroid (PSTVd) via the phloem...
October 19, 2016: Biochimie
Shigeto Sato, Masato Koike, Manabu Funayama, Junji Ezaki, Takahiro Fukuda, Takashi Ueno, Yasuo Uchiyama, Nobutaka Hattori
Kufor-Rakeb syndrome (KRS) is an autosomal recessive form of early-onset parkinsonism linked to the PARK9 locus. The causative gene for KRS is Atp13a2, which encodes a lysosomal type 5 P-type ATPase. We recently showed that KRS/PARK9-linked mutations lead to several lysosomal alterations, including reduced proteolytic processing of cathepsin D in vitro. However, it remains unknown how deficiency of Atp13a2 is connected to lysosomal impairments. To address this issue, we analyzed brain tissues of Atp13a2 conditional-knockout mice, which exhibited characteristic features of neuronal ceroid lipofuscinosis, including accumulation of lipofuscin positive for subunit c of mitochondrial ATP synthase, suggesting that a common pathogenic mechanism underlies both neuronal ceroid lipofuscinosis and Parkinson disease...
October 19, 2016: American Journal of Pathology
Agnieszka Fiszer, Marianna E Ellison-Klimontowicz, Wlodzimierz J Krzyzosiak
Polyglutamine (polyQ) diseases comprise a group of nine genetic disorders that are caused by the expansion of the CAG triplet repeat, which encodes glutamine, in unrelated single genes. Various oligonucleotide (ON)-based therapeutic approaches have been considered for polyQ diseases. The very attractive CAG repeat-targeting strategy offers selective silencing of the mutant allele by directly targeting the mutation site. CAG repeat-targeting miRNA-like siRNAs have been shown to specifically inhibit the mutant gene expression, and their characteristic feature is the formation of mismatches in their interactions with the target site...
October 21, 2016: Acta Biochimica Polonica
Marian Raschke, Bernd-W Igl, Julia Kenny, Joanne Collins, Stephen D Dertinger, Carson Labash, Javed A Bhalli, Cameron C M Tebbe, Kylie M McNeil, Andreas Sutter
The rodent Pig-a assay is an in vivo method for the detection of gene mutation, where lack of glycosylphosphatidylinositol-anchored proteins on the surface of circulating red blood cells (RBCs) serves as a reporter for Pig-a gene mutation. In the case of rats, the frequency of mutant phenotype RBCs is measured via fluorescent anti-CD59 antibodies and flow cytometry. The Pig-a assay meets the growing expectations for novel approaches in animal experimentation not only focusing on the scientific value of the assay but also on animal welfare aspects (3Rs principles), for example, amenable to integration into pivotal rodent 28-day general toxicology studies...
October 22, 2016: Environmental and Molecular Mutagenesis
Lijiang Ma, Wendy K Chung
Group 1 pulmonary hypertension or pulmonary arterial hypertension (PAH) is a rare disease characterized by proliferation and occlusion of small pulmonary arterioles, leading to progressive elevation of pulmonary artery pressure and pulmonary vascular resistance, and right ventricular failure. Historically it has been associated with a high mortality rate, although over the last decade, treatment has improved survival. PAH includes idiopathic PAH (IPAH), heritable PAH (HPAH), and PAH associated with certain medical conditions...
October 22, 2016: Journal of Pathology
Daniel Nichol, Mark Robertson-Tessi, Peter Jeavons, Alexander R A Anderson
Non-genetic variation in phenotypes, or bet-hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet-hedging emerges in the genotype-phenotype mapping through a simple interaction model: a molecular switch. We use simple Chemical Reaction Networks to implement stochastic switches that map gene products to phenotypes and investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet-hedging naturally emerges within this model and is robust to evolutionary loss through mutations to both the expression of individual genes and to the network itself...
October 21, 2016: Genetics
Chanakan Tongsook, Johannes Niederhauser, Elena Kronegger, Grit Straganz, Peter Macheroux
The degradation of histamine catalyzed by the SAM-dependent histamine N-methyltransferase (HNMT) is critically important for the maintenance of neurological processes. Recently, two mutations in the encoding human gene were reported to give rise to dysfunctional protein variants (G60D and L208P) leading to intellectual disability. In the present study, we have expressed eight L208 variants with either apolar (L208F and L208V), polar (L208N and L208T) or charged (L208D, L208H, L208K and L208R) amino acids to define the impact of side chain variations on protein structure and function...
October 18, 2016: Biochimica et Biophysica Acta
Lily Marsden, Lawrence J Jennings, Samantha Gadd, Min Yu, Elizabeth J Perlman, Mariana M Cajaiba
Metanephric stromal tumors are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in metanephric stromal tumors and in other pediatric renal stromal tumors. In this study, 17 metanephric stromal tumors, 22 congenital mesoblastic nephromas and 6 ossifying renal tumors of infancy were selected for BRAF exon 15 testing...
October 18, 2016: Human Pathology
Manisha Balwani, Preeti Singh, Anju Seth, Ekta Malik Debnath, Hetanshi Naik, Dana Doheny, Brenden Chen, Makiko Yasuda, Robert J Desnick
Acute Intermittent Porphyria (AIP), an autosomal dominant inborn error of heme metabolism, typically presents in adulthood, most often in women in the reproductive age group. There are limited reports on the clinical presentation in children, and in contrast to the adults, most of the reported pediatric cases are male. While acute abdominal pain is the most common presenting symptom in children, seizures are commonly seen and may precede the diagnosis of AIP. As an example, we report a 9year old developmentally normal pre-pubertal boy who presented with acute abdominal pain, vomiting and constipation followed by hyponatremia, seizures, weakness and neuropathy...
October 15, 2016: Molecular Genetics and Metabolism
Ron Bochner, Liat Samuelov, Ofer Sarig, Qiaoli Li, Christopher A Adase, Ofer Isakov, Natalia Malchin, Dan Vodo, Ronna Shayevitch, Alon Peled, Benjamin D Yu, Gilad Fainberg, Emily Warshauer, Noam Adir, Noam Erez, Andrea Gat, Yehonatan Gottlieb, Tova Rogers, Mor Pavlovsky, Ilan Goldberg, Noam Shomron, Aileen Sandilands, Linda E Campbell, Stephanie MacCallum, W H Irwin McLean, Gil Ast, Richard L Gallo, Jouni Uitto, Eli Sprecher
Congenital erythroderma is a rare and often life-threatening condition, which has been shown to result from mutations in several genes encoding important components of the epidermal differentiation program. Using whole exome sequencing, we identified in a child with congenital exfoliative erythroderma, hypotrichosis, severe nail dystrophy and failure to thrive, two heterozygous mutations in ABCA12 (c.2956C>T, p.R986W; c.5778+2T>C, p. G1900Mfs*16), a gene known to be associated with 2 forms of ichthyosis, autosomal recessive congenital ichthyosis and harlequin ichthyosis...
October 18, 2016: Journal of Investigative Dermatology
L Baila-Rueda, A Cenarro, I Lamiquiz-Moneo, R Mateo-Gallego, A M Bea-Sanz, S Perez-Calahorra, V Marco-Benedi, F Civeira
Some oxysterols are precursors of bile acid synthesis and play an important role in cholesterol homeostasis. However, if they are involved in the pathogeny of genetic hypercholesterolemia has not been previously explored. We have studied non-cholesterol sterol markers of cholesterol synthesis (lanosterol and desmosterol) and oxysterols (7α-hydroxy-4-cholesten-3-one, 24S-hydroxycholesterol and 27-hydroxycholesterol) in 200 affected subjects with primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH) and 100 normolipemic controls...
October 18, 2016: Journal of Steroid Biochemistry and Molecular Biology
J Chee, B W S R Robinson, R A Holt, J Creaney
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Anti-tumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-PD1/anti-PDL1 antibodies causes tumor regression in around 25% of lung cancer patients. In another approach, the immune system is forced or accelerated to attack the tumour, via augmentation of the anti-tumour response against mutations carried by each lung tumour...
October 18, 2016: Chest
Franziska Hopfner, Dietrich Haubenberger, Wendy R Galpern, Katrina Gwinn, Ashlee Van't Veer, Samantha White, Kailash Bhatia, Charles H Adler, David Eidelberg, William Ondo, Glenn T Stebbins, Caroline M Tanner, Rick C Helmich, Fred A Lenz, Roy V Sillitoe, David Vaillancourt, Jerrold L Vitek, Elan D Louis, Holly A Shill, Matthew P Frosch, Tatiana Foroud, Gregor Kuhlenbäumer, Andrew Singleton, Claudia M Testa, Mark Hallett, Rodger Elble, Günther Deuschl
Essential tremor (ET) is a common cause of significant disability, but its etiologies and pathogenesis are poorly understood. Research has been hampered by the variable definition of ET and by non-standardized research approaches. The National Institute of Neurological Disorders and Stroke (USA) invited experts in ET and related fields to discuss current knowledge, controversies, and gaps in our understanding of ET and to develop recommendations for future research. Discussion focused on phenomenology and phenotypes, therapies and clinical trials, pathophysiology, pathology, and genetics...
October 4, 2016: Parkinsonism & related Disorders
Darwin J Prockop
From the outset, it was apparent that developing new therapies with mesenchymal stem/stromal cells (MSCs) was not a simple or easy task. Among the earliest experiments was administration of MSCs from normal mice to transgenic mice that developed brittle bones because they expressed a mutated gene for type 1 collagen isolated from a patient with osteogenesis imperfecta. The results prompted a clinical trial of MSCs in patients with severe osteogenesis imperfecta. Subsequent work by large numbers of scientists and clinicians has established that, with minor exceptions, MSCs do not engraft or differentiate to a large extent in vivo...
October 18, 2016: Cytotherapy
Kattina Zavala, Michael W Vandewege, Federico G Hoffmann, Juan C Opazo
The study of the evolutionary history of genes related to human disease lies at the interface of evolution and medicine. These studies provide the evolutionary context on which medical researchers should work, and are also useful in providing information to suggest further genetic experiments, especially in model species where genetic manipulations can be made. Here we studied the evolution of the β-adrenoreceptor gene family in vertebrates with the aim of adding an evolutionary framework to the already abundant physiological information...
October 18, 2016: General and Comparative Endocrinology
Hassol Lim, Young-Mi Park, Jong-Keuk Lee, Hyun Taek Lim
OBJECTIVE: To present an efficient and successful application of a single-exome sequencing study in a family clinically diagnosed with X-linked retinitis pigmentosa. DESIGN: Exome sequencing study based on clinical examination data. PARTICIPANTS: An 8-year-old proband and his family. METHODS: The proband and his family members underwent comprehensive ophthalmologic examinations. Exome sequencing was undertaken in the proband using Agilent SureSelect Human All Exon Kit and Illumina HiSeq 2000 platform...
October 2016: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
S Micheletti, F Palestra, P Martelli, P Accorsi, J Galli, L Giordano, V Trebeschi, E Fazzi
BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopment disorder resulting from deficient expression or function of the maternally inherited allele of UBE3A gene. The aim of the study is to attempt at providing a detailed definition of neurodevelopmental profile in AS, with particular regard to motor, cognitive, communicative, behavioural and neurovisual, features by using standardized instruments. METHOD: A total of ten subjects aged from 5 to 11 years (4 males and 6 females) with molecular confirmed diagnosis of AS (7 15q11...
October 21, 2016: Italian Journal of Pediatrics
Nadia A Akawi, Salma Ben-Salem, Jozef Hertecant, Anne John, Thachillath Pramathan, Praseetha Kizhakkedath, Bassam R Ali, Lihadh Al-Gazali
BACKGROUND: The group of ELAC2-related encephalomyopathies is a recent addition to the rapidly growing heterogeneous mitochondrial disorders. RESULTS: We describe a highly inbred consanguineous Pakistani family with multiple affected children in 2 branches exhibiting moderately severe global developmental delay. Using homozygosity mapping, we mapped the phenotype in this family to a single locus on chromosome 17. In addition, whole-exome sequencing identified a homozygous splicing mutation (c...
October 21, 2016: Orphanet Journal of Rare Diseases
S Lühl, H Bode, W Schlötzer, M Bartsakoulia, R Horvath, A Abicht, M Stenzel, J Kirschner, S C Grünert
BACKGROUND: Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease caused by mutations in the RARS2 gene. RARS2 encodes mitochondrial arginyl transfer RNA synthetase, an enzyme involved in mitochondrial protein translation. A total of 27 patients from 14 families have been reported so far. Characteristic clinical features comprise neonatal lactic acidosis, severe encephalopathy, intractable seizures, feeding problems and profound developmental delay. Most patients show typical neuroradiologic abnormalities including cerebellar hypoplasia and progressive pontocerebellar atrophy...
October 21, 2016: Orphanet Journal of Rare Diseases
Tshifhiwa Magoro, George Gachara, Lufuno Mavhandu, Emmaculate Lum, Helen K Kimbi, Roland N Ndip, Pascal Bessong
BACKGROUND: HBV and HIV share similar transmission routes. Concurrent infection with the two viruses usually results in more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Further, this co-infection may lead to cross-resistance between HIV and HBV drugs and increased liver injury, either due to direct hepatotoxicity or drug-related immune-reconstitution hepatitis. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to guide patient management...
October 21, 2016: Virology Journal
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