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Published in: Journal of Inherited Metabolic Disease 3/2012

01-05-2012 | Original Article

Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2

Authors: Emma Glamuzina, Ruth Brown, Kieran Hogarth, Dawn Saunders, Isabelle Russell-Eggitt, Matthew Pitt, Carlos de Sousa, Shamima Rahman, Garry Brown, Stephanie Grunewald

Published in: Journal of Inherited Metabolic Disease | Issue 3/2012

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Abstract

Pontocerebellar hypoplasia type 6 (PCH6) (MIM #611523) is a recently described disorder caused by mutations in RARS2 (MIM *611524), the gene encoding mitochondrial arginyl-transfer RNA (tRNA) synthetase, a protein essential for translation of all mitochondrially synthesised proteins. This case confirms that progressive cerebellar and cerebral atrophy with microcephaly and complex epilepsy are characteristic features of PCH6. Additional features of PCH subtypes 2 and 4, including severe dystonia, optic atrophy and thinning of the corpus callosum, are demonstrated. Congenital lactic acidosis can be present, but respiratory chain dysfunction may be mild or absent, suggesting that disordered mitochondrial messenger RNA (mRNA) translation may not be the only mechanism of impairment or that a secondary mechanism exists to allow some translation. We report two novel mutations and expand the phenotypic spectrum of this likely underdiagnosed PCH variant, where recognition of the characteristic neuroradiological phenotype could potentially expedite genetic diagnosis and limit invasive investigations.
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Metadata
Title
Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2
Authors
Emma Glamuzina
Ruth Brown
Kieran Hogarth
Dawn Saunders
Isabelle Russell-Eggitt
Matthew Pitt
Carlos de Sousa
Shamima Rahman
Garry Brown
Stephanie Grunewald
Publication date
01-05-2012
Publisher
Springer Netherlands
Published in
Journal of Inherited Metabolic Disease / Issue 3/2012
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-011-9413-6

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