Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients.

Journal of Inherited Metabolic Disease
Denise CassandriniEnrico Bertini

Abstract

Recessive mutations in the mitochondrial arginyl-transfer RNA synthetase (RARS2) gene have been associated with early onset encephalopathy with signs of oxidative phosphorylation defects classified as pontocerebellar hypoplasia 6. We describe clinical, neuroimaging and molecular features on five patients from three unrelated families who displayed mutations in RARS2. All patients rapidly developed a neonatal or early-infantile epileptic encephalopathy with intractable seizures. The long-term follow-up revealed a virtual absence of psychomotor development, progressive microcephaly, and feeding difficulties. Mitochondrial respiratory chain enzymes in muscle and fibroblasts were normal in two. Blood and CSF lactate was abnormally elevated in all five patients at early stages while appearing only occasionally abnormal with the progression of the disease. Cerebellar vermis hypoplasia with normal aspect of the cerebral and cerebellar hemispheres appeared within the first months of life at brain MRI. In three patients follow-up neuroimaging revealed a progressive pontocerebellar and cerebral cortical atrophy. Molecular investigations of RARS2 disclosed the c.25A>G/p.I9V and the c.1586+3A>T in family A, the c.734G>A/p.R245Q and the c.1...Continue Reading

References

Nov 1, 1984·Analytical Biochemistry·G G ChangH Y Wang
Apr 1, 1983·Analytical Biochemistry·G G ChangT M Huang
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·J A Enríquez, G Attardi
Jan 1, 1996·Methods in Enzymology·J A Enríquez, G Attardi
Feb 7, 2001·The Journal of Biological Chemistry·J R DickinsonM J Hewlins
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Aug 27, 2005·Mitochondrion·Xenia B Hom, Joel E Lavine
Feb 18, 2006·Biochemical and Biophysical Research Communications·Denise CassandriniClaudio Bruno
Jan 8, 2008·Journal of Medical Genetics·H A L TuppenR W Taylor
Feb 5, 2008·Molecular Genetics and Metabolism·UNKNOWN Mitochondrial Medicine Society's Committee on DiagnosisRobert K Naviaux
Jun 5, 2008·FEMS Microbiology Reviews·Corinne D Hausmann, Michael Ibba
Aug 20, 2008·Nature Genetics·Birgit S BuddeFrank Baas
Sep 5, 2008·Annual Review of Genomics and Human Genetics·Anthony Antonellis, Eric D Green
Feb 5, 2009·Journal of Internal Medicine·R McFarland, D M Turnbull
Apr 22, 2009·Annual Review of Microbiology·Jiqiang LingMichael Ibba
Aug 4, 2009·American Journal of Human Genetics·Paul RenbaumEphrat Levy-Lahad
May 22, 2010·Journal of Inherited Metabolic Disease·Salvatore Dimauro
Jul 17, 2010·American Journal of Medical Genetics. Part a·Julia RankinGarry Brown
Jul 24, 2010·Lancet Neurology·Robert McFarlandDouglass M Turnbull
Sep 8, 2010·Developmental Disabilities Research Reviews·Seth D FriedmanRussell P Saneto
Sep 8, 2010·Developmental Disabilities Research Reviews·Lee-Jun C Wong
Oct 6, 2010·American Journal of Human Genetics·Orly AgamyOhad S Birk
Oct 19, 2010·Brain : a Journal of Neurology·Yasmin NamavarBwee Tien Poll-The
Oct 20, 2010·Neurology·D CassandriniE Bertini
Nov 30, 2010·Neuromuscular Disorders : NMD·Z M A Chrzanowska-LightowlersR N Lightowlers
May 17, 2011·Journal of Child Neurology·Célia NogueiraFilippo M Santorelli

❮ Previous
Next ❯

Citations

Mar 22, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Amy C GoldsteinJodie M Vento
Mar 19, 2014·International Journal of Cell Biology·Daria DiodatoValeria Tiranti
Feb 22, 2013·EMBO Molecular Medicine·Peng Yao, Paul L Fox
Feb 26, 2013·Molecular Genetics and Metabolism·Svetlana Konovalova, Henna Tyynismaa
Mar 14, 2016·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Daniella NishriDorit Lev
Jun 14, 2014·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Sabine Rudnik-SchönebornKlaus Zerres
Apr 12, 2016·Epilepsia·Adeline NgohManju A Kurian
Apr 15, 2016·American Journal of Medical Genetics. Part a·Hülya KayseriliRasim Özgür Rosti
Mar 27, 2015·Journal of Human Genetics·Zejuan LiDaniela del Gaudio
Dec 17, 2014·The Cerebellum·Eugen BoltshauserAndrea Poretti
Oct 22, 2013·Biochimica Et Biophysica Acta·Mara DoimoLeonardo Salviati
May 5, 2016·Molecular Genetics and Metabolism Reports·Josef Finsterer, Sinda Zarrouk-Mahjoub
Jan 8, 2015·European Journal of Human Genetics : EJHG·Maria Andrea DesbatsLeonardo Salviati
Sep 21, 2013·Archives of Disease in Childhood·Katherina KastrissianakisTony McShane
May 24, 2017·RNA Biology·Jana Ognjenović, Miljan Simonović
Jun 22, 2017·Human Molecular Genetics·Rebecca Meyer-Schuman, Anthony Antonellis
Jul 15, 2018·The Journal of Biological Chemistry·Ligia Elena González-SerranoMarie Sissler
May 18, 2019·American Journal of Medical Genetics. Part a·Siddharth SrivastavaSakkuBai Naidu
May 16, 2020·The Cerebellum·Christina T RüschEugen Boltshauser
May 13, 2017·Orphanet Journal of Rare Diseases·Alessia NascaDaniele Ghezzi
Jul 8, 2018·Essays in Biochemistry·Veronika BoczonadiRita Horvath
Jul 6, 2019·Nucleic Acids Research·Lindsey Van HauteMichal Minczuk
Jun 16, 2018·Orphanet Journal of Rare Diseases·Tessa van DijkBwee Tien Poll-The
Mar 30, 2019·Neurogenetics·Andrea AccogliMyriam Srour
Jul 22, 2018·Essays in Biochemistry·Mario MascalchiRenzo Guerrini
Feb 4, 2021·The Cerebellum·Andrea AccogliMyriam Srour
May 1, 2021·International Journal of Molecular Sciences·Sonia FigucciaPaola Goffrini
May 12, 2021·Molecular Genetics and Metabolism·Charles-Joris RouxNathalie Boddaert
Oct 31, 2021·Epilepsia Open·Guillem de Valles-IbáñezLynette G Sadleir

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.