OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: A truncating<em> PET100</em> variant causing fatal infantile lactic acidosis and isolated cytochrome <em>c</em> oxidase deficiency.

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Oláhová, M.* ; Haack, T.B. ; Alston, C.L.* ; Houghton, J.A.* ; He, L.* ; Morris, A.A.* ; Brown, G.K.* ; McFarland, R.* ; Chrzanowska-Lightowlers, Z.M.* ; Lightowlers, R.N.* ; Prokisch, H. ; Taylor, R.W.*

A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency.

Eur. J. Hum. Genet. 23, 935-939 (2015)
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Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene.
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Leigh-syndrome; Mitochondrial Disease; Complex Iv; Mutation; Chain; Surf1; Heme; Gene; Biogenesis; Phenotypes
ISSN (print) / ISBN 1018-4813
e-ISSN 1476-5438
Journal European Journal of Human Genetics
Quellenangaben Volume: 23, Issue: 7, Pages: 935-939 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)