Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations

Journal of Neuropathology and Experimental Neurology

Volumn 74, Issue 7, 2015, Pages 688-703

  Lax, Nichola Z ^a   Alston, Charlotte L ^a   Schon, Katherine ^b   Park, Soo Mi ^b   Krishnakumar, Deepa ^c   He, Langping ^a   Falkous, Gavin ^a   Ogilvy Stuart, Amanda ^d   Lees, Christoph ^e   King, Rosalind H ^f   Hargreaves, Iain P ^g   Brown, Garry K ^h   McFarland, Robert ^a   Dean, Andrew F ^b   Taylor, Robert W ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^c ADDENBROOKE S HOSPITAL   (United Kingdom)

^d Rosie Maternity Hospital   (United Kingdom)

^e QUEEN CHARLOTTE S AND CHELSEA HOSPITAL   (United Kingdom)

^f UNIVERSITY COLLEGE LONDON   (United Kingdom)

^g NATIONAL HOSPITAL FOR NEUROLOGY AND NEUROSURGERY   (United Kingdom)

^h OXFORD UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Mitochondrial disease; Pontocerebellar hypoplasia type 6; RARS2; Respiratory chain deficiency

Indexed keywords

ARGININE TRANSFER RNA LIGASE; CALCIUM; CYTOCHROME C OXIDASE; AMINOACYLTRANSFERASE; ARGINYLTRANSFERASE;

APGAR SCORE; ARTICLE; ASSISTED VENTILATION; AUTOSOMAL RECESSIVE INHERITANCE; BRAIN TISSUE; CALCIUM BLOOD LEVEL; CARDIOMYOPATHY; CASE REPORT; CYTOCHROME C OXIDASE DEFICIENCY; ENZYME HISTOCHEMISTRY; FEMALE; FETUS ELECTROCARDIOGRAPHY; FETUS HYDROPS; GENE MUTATION; GENETIC DISORDER; HETEROZYGOTE; HISTOLOGY; HUMAN; HUMAN TISSUE; HYDRAMNIOS; IMMUNOHISTOCHEMISTRY; LUNG HYPOPLASIA; MITOCHONDRIAL ENCEPHALOMYOPATHY; MOLECULAR GENETICS; MULTISYSTEM RESPIRATORY CHAIN DEFICIENCY; NEUROLOGIC EXAMINATION; NEUROPATHOLOGY; NEWBORN; NUCHAL TRANSLUCENCY MEASUREMENT; NUCLEAR MAGNETIC RESONANCE IMAGING; OLIVOPONTOCEREBELLAR ATROPHY; PRIORITY JOURNAL; BRAIN; COMPLICATION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; FETUS; GENETICS; METABOLISM; MOLECULAR BIOLOGY; MUSCLE; MUTATION; PATHOLOGY; POSTMORTEM CHANGE; PREGNANCY;

AMINOACYLTRANSFERASES; BRAIN; CARDIOMYOPATHIES; ELECTRON TRANSPORT COMPLEX IV; FEMALE; FETUS; HUMANS; HYDROPS FETALIS; INFANT, NEWBORN; MAGNETIC RESONANCE IMAGING; MITOCHONDRIAL DISEASES; MOLECULAR BIOLOGY; MUSCLES; MUTATION; OLIVOPONTOCEREBELLAR ATROPHIES; POSTMORTEM CHANGES; PREGNANCY;

EID: 84934312290     PISSN: 00223069     EISSN: 15546578     Source Type: Journal    
DOI: 10.1097/NEN.0000000000000209     Document Type: Article

References (32)

1. Skladal D, Halliday J, Thorburn DR. Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 2003;126:1905-12
2. Taylor RW, Pyle A, Griffin H, et al. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA 2014;312:68-77
3. Diodato D, Ghezzi D, Tiranti V. The mitochondrial aminoacyl tRNA synthetases: genes and syndromes. Int J Cell Biol 2014;2014:787956
4. Smits P, Smeitink J, van den Heuvel L. Mitochondrial translation and beyond: processes implicated in combined oxidative phosphorylation deficiencies. J Biomed Biotech 2010;2010:737385
5. Edvardson S, Shaag A, Kolesnikova O, et al. Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. American J Hum Gen 2007;81:857-62
6. Rankin J, Brown R, Dobyns WB, et al. Pontocerebellar hypoplasia type 6: A British case with PEHO-like features. AmJ Med Gen Part A 2010;152A:2079-84
7. Namavar Y, Barth PG, Kasher PR, et al. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain 2011;134:143-56
8. Kastrissianakis K, Anand G, Quaghebeur G, et al. Subdural effusions and lack of early pontocerebellar hypoplasia in siblings with RARS2 mutations. Arch Dis Child 2013;98:1004-7
9. Glamuzina E, Brown R, Hogarth K, et al. Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2. J Inher Metab Dis 2012;35:459-67
10. Cassandrini D, Cilio MR, Bianchi M, et al. Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients. J Inher Metab Dis 2013;36:43-53
11. Joseph JT, Innes AM, Smith AC, et al. Neuropathologic features of pontocerebellar hypoplasia type 6. J Neuropathol Exp Neurol 2014;73:1009-25
12. Wright D, Kagan KO, Molina FS, et al. A mixture model of nuchal translucency thickness in screening for chromosomal defects. Ultrasound Obstet Gynecol 2008;31:376-83
13. Old SL, Johnson MA. Methods of microphotometric assay of succinate dehydrogenase and cytochrome c oxidase activities for use on human skeletal muscle. Histochem J 1989;21:545-55
14. Lax NZ, Gnanapavan S, Dowson SJ, et al. Early-onset cataracts, spastic paraparesis, and ataxia caused by a novel mitochondrial tRNAGlu (MT-TE) gene mutation causing severe complex I deficiency: a clinical, molecular, and neuropathologic study. J Neuropathol Exp Neurol 2013;72:164-75
15. Untergasser A, Cutcutache I, Koressaar T, et al. Primer3 - new capabilities and interfaces. Nucleic Acids Res 2012;40:e115
16. Noensie EN, Dietz HC. A strategy for disease gene identification through nonsense-mediated mRNA decay inhibition. Nature Biotechnol 2001;19:434-9
17. Betts J, Jaros E, Perry RH, et al. Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement. Neuropathol Appl Neurobiol 2006;32:359-73
18. Guihard-Costa AM, Larroche JC. Differential growth between the fetal brain and its infratentorial part. Early Hum Devel 1990;23:27-40
19. Schiff M, Ogier de Baulny H, Lombes A. Neonatal cardiomyopathies and metabolic crises due to oxidative phosphorylation defects. Sem Fetal Neonatal Med 2011;16:216-21
20. Lopaschuk GD, Jaswal JS. Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal maturation. J Cardiovasc Pharm 2010;56:130-40
21. Kopajtich R, Nicholls TJ, Rorbach J, et al. Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy. Am J Hum Gen 2014;95:708-20
22. Ghezzi D, Baruffini E, Haack TB, et al. Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis. Am J Hum Gen 2012;90:1079-87
23. Gotz A, Tyynismaa H, Euro L, et al. Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy. Am J Hum Gen 2011;88:635-42
24. Grefsheim SF, Whitmore SC, Rapp BA, et al. The informationist: building evidence for an emerging health profession. J Med Libr Assoc 2010;98:147-56
25. Bonifert T, Karle KN, Tonagel F, et al. Pure and syndromic optic atrophy explained by deep intronic OPA1 mutations and an intralocus modifier. Brain 2014;137:2164-77
26. Larsell O, Jansen J, Korneliussen HK, Mugnaini E. The Comparative Anatomy and Histology of the Cerebellum: The Human Cerebellum, Cerebellar Connections, and Cerebellar Cortex. Minneapolis, MN. Minnesota University Press, 1972
27. Hakonen AH, Goffart S, Marjavaara S, et al. Infantile-onset spinocerebellar ataxia and mitochondrial recessive ataxia syndrome are associated with neuronal complex I defect and mtDNA depletion. Hum Molec Gen 2008;17:3822-35
28. Quintana A, Kruse SE, Kapur RP, et al. Complex I deficiency due to loss of Ndufs4 in the brain results in progressive encephalopathy resembling Leigh syndrome. Proc Natl Acad Sci USA 2010;107:10996-1001
29. Lax NZ, Hepplewhite PD, Reeve AK, et al. Cerebellar ataxia in patients with mitochondrial DNA disease: a molecular clinicopathological study. J Neuropathol Exp Neurol 2012;71:148-61
30. Limperopoulos C, Soul JS, Gauvreau K, et al. Late gestation cerebellar growth is rapid and impeded by premature birth. Pediatrics 2005;115:688-95
31. Lai MC, Yang SN. Perinatal hypoxic-ischemic encephalopathy. J Biomed Biotechnol 2011;2011:609813
32. Kasher PR, Namavar Y, van Tijn P, et al. Impairment of the tRNA-splicing endonuclease subunit 54 (tsen54) gene causes neurological abnormalities and larval death in zebrafish models of pontocerebellar hypoplasia. Hum Molec Gen 2011;20:1574-84