13 results on '"Akman H.O."'
Search Results
2. Placental Involvement in Glycogen Storage Disease Type IV
- Author
-
Konstantinidou, A.E., Anninos, H., Dertinger, S., Nonni, A., Petersen, M., Karadimas, C., Havaki, S., Marinos, E., Akman, H.O., DiMauro, S., and Patsouris, E.
- Published
- 2008
- Full Text
- View/download PDF
3. Placental Involvement in Glycogen Storage Disease Type IV
- Author
-
Konstantinidou, A.E. Anninos, H. Dertinger, S. Nonni, A. Petersen, M. Karadimas, C. Havaki, S. Marinos, E. Akman, H.O. DiMauro, S. Patsouris, E.
- Abstract
Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by glycogen branching enzyme (GBE) deficiency and resulting in the storage of abnormal glycogen (polyglucosan). Prenatal diagnosis is based on biochemical assay of GBE activity or on mutation analysis, but polyglucosan can also be identified histologically in fetal tissues. We document placental involvement at 25 and 35 weeks of gestation in two cases with genetically confirmed GSD IV. Intracellular inclusions were seen mainly in the extravillous trophoblast. Our findings suggest the possibility of prenatal diagnosis by histological evaluation of placental biopsies. © 2008 Elsevier Ltd. All rights reserved.
- Published
- 2008
4. P17.19 Deoxypyrimidine monophosphates treatment for thymidine kinase 2 deficiency
- Author
-
Garone, C., primary, Garcia-Diaz, B., additional, Emmanuele, V., additional, Tadesse, S., additional, Akman, H.O., additional, Tanji, K., additional, Quinzii, C.M., additional, and Hirano, M., additional
- Published
- 2013
- Full Text
- View/download PDF
5. P.5.19 Fhl1 W122S knock-in mice manifest late-onset mild myopathy
- Author
-
Emmanuele, V., primary, Kubota, A., additional, Garcia-Diaz, B., additional, Garone, C., additional, Akman, H.O., additional, Tanji, K., additional, Quinzii, C.M., additional, and Hirano, M., additional
- Published
- 2013
- Full Text
- View/download PDF
6. G.P.16.03. A clinical and genetic study of 2 patients with myopathy and phosphorylase kinase deficiency (glycogenosis type VIII)
- Author
-
Echaniz-Laguna, A., primary, Akman, H.O., additional, Mohr, M., additional, Tranchant, C., additional, Maire, I., additional, and Mauro, S. di, additional
- Published
- 2008
- Full Text
- View/download PDF
7. G.P.16.04. Branching enzyme deficiency should be considered in the differential diagnosis of severe congenital hypotonia
- Author
-
Taratuto, A.L., primary, Akman, H.O., additional, Saccoliti, M., additional, Riudavets, M., additional, Arakaki, N., additional, Fernández, M., additional, Mesa, L., additional, Sevlever, G., additional, Goebel, H., additional, and Di Mauro, S., additional
- Published
- 2008
- Full Text
- View/download PDF
8. Muscle phosphorylase kinase deficiency
- Author
-
Preisler, N., Ørngreen, M.C., Echaniz-Laguna, A., Laforet, P., Lonsdorfer-Wolf, E., Doutreleau, S., Geny, B., Akman, H.O., DiMauro, S., and Vissing, J.
- Abstract
To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).
- Published
- 2012
- Full Text
- View/download PDF
9. Fhl1 W122S causes loss of protein function and late-onset mild myopathy
- Author
-
Catarina M. Quinzii, Shingo Kariya, Michio Hirano, Akatsuki Kubota, Valentina Emmanuele, Shunichi Homma, Daniel Sánchez-Gutiérrez, Kurenai Tanji, Luis M. Escudero, Hasan O. Akman, Caterina Garone, Beatriz Garcia-Diaz, Emmanuele V., Kubota A., Garcia-Diaz B., Garone C., Akman H.O., Sanchez-Gutierrez D., Escudero L.M., Kariya S., Homma S., Tanji K., Quinzii C.M., Hirano M., Ministerio de Ciencia e Innovación (España), Caffarelli Family Study Research Foundation, and Muscular Dystrophy Association (US)
- Subjects
Male ,Cytoplasmic inclusion ,Kemizygosity ,Myopathy ,Muscle Proteins ,Western blotting ,Mice ,Forelimb ,Missense mutation ,Gene Knock-In Techniques ,Skeletal muscles ,Muscular dystrophy ,Age of Onset ,Genetics (clinical) ,Intracellular Signaling Peptides and Proteins ,Cardiac muscle ,Articles ,General Medicine ,Anatomy ,LIM Domain Proteins ,Muscular Dystrophy, Emery-Dreifuss ,Muscle atrophy ,medicine.anatomical_structure ,Phenotype ,Knockin ,Female ,medicine.symptom ,Human ,medicine.medical_specialty ,Heterozygote ,Mutation, Missense ,Biology ,Muscle Protein ,Gene Knock-In Technique ,Internal medicine ,Genetics ,medicine ,Animals ,Humans ,Muscle, Skeletal ,Molecular Biology ,Hemizygote ,Animal ,Muscular Dystrophy, Emery-Dreifu ,LIM Domain Protein ,Myocardium ,Muscle weakness ,Mice mice ,medicine.disease ,FHL1 ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,Intracellular Signaling Peptides and Protein ,Mutation - Abstract
Emmanuele, Valentina et al., © The Author 2014. Published by Oxford University Press. All rights reserved. A member of the four-and-a-half-LIM (FHL) domain protein family, FHL1, is highly expressed in human adult skeletal and cardiac muscle. Mutations in FHL1 have been associated with diverse X-linked muscle diseases: scapuloperoneal (SP) myopathy, reducing body myopathy, X-linked myopathy with postural muscle atrophy, rigid spine syndrome (RSS) and Emery-Dreifuss muscular dystrophy. In 2008, we identified a missense mutation in the second LIM domain of FHL1 (c.365 G>C, p.W122S) in a family with SP myopathy. We generated a knock-in mouse model harboring the c.365 G>C Fhl1 mutation and investigated the effects of this mutation at three time points (3-5 months, 7-10 months and 18-20 months) in hemizygous male and heterozygous female mice. Survival was comparable in mutant and wild-type animals. We observed decreased forelimb strength and exercise capacity in adult hemizygous male mice starting from 7 to 10 months of age. Western blot analysis showed absence of Fhl1 in muscle at later stages. Thus, adult hemizygous male, but not heterozygous female, mice showed a slowly progressive phenotype similar to human patients with late-onset muscle weakness. In contrast to SP myopathy patients with the FHL1 W122S mutation, mutant mice did not manifest cytoplasmic inclusions (reducing bodies) in muscle. Because muscle weakness was evident prior to loss of Fhl1 protein and without reducing bodies, our findings indicate that loss of function is responsible for the myopathy in the Fhl1 W122S knock-in mice., This work has been supported by the Muscular Dystrophy Association (MDA), grant number 115567; and by the Caffarelli Family Study Research (CSFR) Foundation, Inc. L.M.E. and D.S.-G. are supported by the Ramón y Cajal program (PI13/01347), and the Spanish government grants: BFU2011-25734 and PI13/01347.
- Published
- 2015
10. Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency
- Author
-
Michio Hirano, Hasan O. Akman, Kurenai Tanji, Luis C. López, Catarina M. Quinzii, Saba Tadesse, Beatriz Garcia-Diaz, Caterina Garone, Valentina Emmanuele, Garone C., Garcia-Diaz B., Emmanuele V., Lopez L.C., Tadesse S., Akman H.O., Tanji K., Quinzii C.M., Hirano M., Garone, Caterina [0000-0003-4928-1037], and Apollo - University of Cambridge Repository
- Subjects
Mitochondrial DNA ,Mitochondrial Diseases ,Mutant ,Encephalomyopathy ,Biology ,Thymidine Kinase ,Gene Knock-In Technique ,chemistry.chemical_compound ,Mice ,encephalomyopathy ,Mitochondrial Disease ,Thymidine Monophosphate ,Animals ,Gene Knock-In Techniques ,Gene ,Research Articles ,Deoxythymidine Monophosphate ,Thymidine monophosphate ,therapy ,Animal ,deoxythymidine monophosphate ,Deoxycytidine monophosphate ,Deoxycytidine Monophosphate ,Molecular biology ,Phenotype ,Survival Analysis ,3. Good health ,Treatment Outcome ,chemistry ,Thymidine kinase ,Molecular Medicine ,Deoxycytidine ,Survival Analysi ,Therapy - Abstract
Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2−/−) knock‐in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13‐day‐old Tk2−/− mice treated with dCMP+dTMP 200 mg/kg/day each (Tk2−/−200dCMP/dTMP) demonstrated that in mutant animals, the compounds raise dTTP concentrations, increase levels of mtDNA, ameliorate defects of mitochondrial respiratory chain enzymes, and significantly prolong their lifespan (34 days with treatment versus 13 days untreated). A second trial of dCMP+dTMP each at 400 mg/kg/day showed even greater phenotypic and biochemical improvements. In conclusion, dCMP/dTMP supplementation is the first effective pharmacologic treatment for Tk2 deficiency., This work was supported by research grants from the Muscular Dystrophy Association (MH) and the Associazione Malattie Metaboliche Congenite ereditarie (AMMeC) (CG) as well as by the Arturo Estopinan TK2 Research Fund (MH and CG) and the Marriott Mitochondrial Disease Clinic Research Fund (MMDCRF) (MH). MH acknowledges support from NIH grants (P01 HD32062, R01 HD057543, and R01 HD056103 from NICHD) and the Office of Dietary Supplements, as well as U54 NS078059 from NINDS and NICHD. LCL acknowledges support from CEIBioTic‐University of Granada, RYC‐2011‐07643, and RETICEF (Spain).
- Published
- 2014
11. P.5.19 Fhl1 W122S knock-in mice manifest late-onset mild myopathy.
- Author
-
Kubota, A., Garcia-Diaz, B., Garone, C., Akman, H.O., Tanji, K., Quinzii, C.M., and Hirano, M.
- Subjects
- *
MUSCLE diseases , *LABORATORY mice , *SKELETAL muscle , *GENE expression , *MUSCLE growth , *CELL differentiation , *BIOMECHANICS , *PHYSIOLOGICAL stress - Abstract
FHL1 is a member of the four-and-a half-LIM (FHL) domain protein family and it is highly expressed in adult human skeletal muscle. It is believed to participate in sarcomere assembly, muscle growth and differentiation, and in the biomechanical stress responses. Mutations in FHL1 gene have been associated with different myopathies, including reducing body myopathy, scapuloperoneal (SP) myopathy, X-linked myopathy with postural muscle atrophy, rigid spine syndrome (RSS), and Emery-Dreifuss muscular dystrophy. In 2008, we identified a missense mutation in the second LIM domain of FHL1 (c.365 G>C, p.W122S) in a family with SP myopathy. We have generated a knock-in mouse model harboring the c.365 G>C Fhl1 mutation and have investigated the effects of this mutation at pre-symptomatic, phenotypic-onset, and late-stage of the disease, in hemizygous males and heterozygous females mice. Survival was comparable in mutant and wild-type animals. Adult hemizygous males mice showed a slowly progressive phenotype similar to human patients with relatively late-onset muscle weakness. In particular, we observed reduced forelimb strength and exercise capacity. Western blot analysis showed absence of FHL1 protein in muscle of hemizygous males at advanced stages. This animal model may help to elucidate the role of FHL1 in skeletal muscle and the pathomechanism of FHL1 mutations in X-linked dominant scapuloperoneal myopathy. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
12. P17.19 Deoxypyrimidine monophosphates treatment for thymidine kinase 2 deficiency.
- Author
-
Garcia-Diaz, B., Emmanuele, V., Tadesse, S., Akman, H.O., Tanji, K., Quinzii, C.M., and Hirano, M.
- Subjects
- *
PYRIMIDINES , *PHOSPHATES , *THYMIDINE , *ENZYME deficiency , *GENETIC mutation , *NEUROMUSCULAR diseases , *MITOCHONDRIAL DNA , *THERAPEUTICS - Abstract
Autosomal recessive TK2 mutations have been associated with severe depletion of mitochondrial DNA (mtDNA) and devastating neuromuscular diseases in infants and children, and with mtDNA multiple deletions and progressive external ophthalmoplegia in adults. Similar to other mitochondrial disorders, only supportive treatments are available for TK2 deficiency. We generated a Tk2 H126N knock-in mouse model that manifests a phenotype strikingly similar to the human infantile encephalomyopathy. We demonstrated that lack of Tk2 activity cause nucleotide pools unbalance with severe reductions of deoxypyrimidine triphosphates (dTTP and dCTP) in brain and liver, leading to reduction of mtDNA copy number. To bypass Tk2 deficiency, we administered deoxypyrimidine monophosphates (dCMP+dTMP) to Tk2 knock-in mice by oral gavage from postnatal day 4, when mutant mice are biochemically affected but phenotypically normal. Assessment of 13-day old Tk2−/− mice treated with dCMP+dTMP 200mg/kg/day each demonstrated that in mutant animals, the compounds: raise dCMP+dTMP concentrations; increase levels of mtDNA, augment quantity and activities of mitochondrial respiratory chain enzyme; and significantly prolong their lifespan (34days with treatment vs 13days untreated). A second trial of dCMP+dTMP at 400mg/kg/day showed even greater phenotypic and biochemical improvements. No adverse effects were observed with both doses of dCMP+dTMP. Oral dCMP+dTMP supplementation is the first effective and safe treatment for TK2 deficiency in mice. This treatment can potentially be applied to patients. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
13. Macrocytic Anemia and Mitochondriopathy Resulting from a Defect in Sideroflexin 4
- Author
-
Diana S. Branco, Vamsi K. Mootha, Tim M. Strom, Salvatore DiMauro, Barry H. Paw, H. Orhan Akman, Jonathan N. Thon, Sarah E. Calvo, Laura S. Kremer, Jeffrey D. Cooney, Skadi Beblo, Joseph E. Italiano, Carla M. Koehler, Gordon J. Hildick-Smith, Holger Prokisch, Andreas Merkenschlager, Yvette Y. Yien, Peter Freisinger, Tobias B. Haack, Nicholas C. Huston, Daniel S. Lieber, Caterina Garone, Dhvanit I. Shah, Matthew L. Freedman, Thomas Meitinger, Non Miyata, M. Alice Donati, Hildick-Smith G.J., Cooney J.D., Garone C., Kremer L.S., Haack T.B., Thon J.N., Miyata N., Lieber D.S., Calvo S.E., Akman H.O., Yien Y.Y., Huston N.C., Branco D.S., Shah D.I., Freedman M.L., Koehler C.M., Italiano Jr. J.E., Merkenschlager A., Beblo S., Strom T.M., Meitinger T., Freisinger P., Donati M.A., Prokisch H., Mootha V.K., DiMauro S., and Paw B.H.
- Subjects
Mitochondrial Diseases ,Macrocytic ,medicine.disease_cause ,Medical and Health Sciences ,0302 clinical medicine ,Mitochondrial Disease ,Erythropoiesi ,Genetics(clinical) ,Erythropoiesis ,Exome ,Anemia, Macrocytic ,Child ,Inner mitochondrial membrane ,Membrane Protein ,Zebrafish ,Genetics (clinical) ,Exome sequencing ,Pediatric ,Genetics & Heredity ,0303 health sciences ,Mutation ,Anemia ,Hematology ,Biological Sciences ,3. Good health ,Gene Knockdown Techniques ,Female ,Human ,Adolescent ,Mitochondrial disease ,Biology ,Mitochondrial Proteins ,03 medical and health sciences ,Report ,Genetics ,medicine ,Mitochondrial Protein ,Animals ,Humans ,030304 developmental biology ,Animal ,Membrane Proteins ,medicine.disease ,biology.organism_classification ,Molecular biology ,Gene Knockdown Technique ,Immunology ,Macrocytic anemia ,030217 neurology & neurosurgery - Abstract
We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. In vitro and in vivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia. © 2013 by The American Society of Human Genetics. All rights reserved.
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.