Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome.

TitleLack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome.
Publication TypeJournal Article
Year of Publication2012
AuthorsMayr, JA, Haack, TB, Graf, E, Zimmermann, FA, Wieland, T, Haberberger, B, Superti-Furga, A, Kirschner, J, Steinmann, B, Baumgartner, MR, Moroni, I, Lamantea, E, Zeviani, M, Rodenburg, RJ, Smeitink, J, Strom, TM, Meitinger, T, Sperl, W, Prokisch, H
JournalAm J Hum Genet
Volume90
Issue2
Pagination314-20
Date Published2012 Feb 10
ISSN1537-6605
KeywordsAdult, Alleles, Cardiomyopathies, Cataract, Child, Codon, Nonsense, Exome, Female, Heterozygote, Humans, Infant, Infant, Newborn, Male, Mitochondria, Mitochondrial ADP, ATP Translocases, Mitochondrial Proteins, Muscles, Phenotype, Phospholipids, Phosphotransferases (Alcohol Group Acceptor), Young Adult
Abstract

Exome sequencing of an individual with congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis, all typical symptoms of Sengers syndrome, discovered two nonsense mutations in the gene encoding mitochondrial acylglycerol kinase (AGK). Mutation screening of AGK in further individuals with congenital cataracts and cardiomyopathy identified numerous loss-of-function mutations in an additional eight families, confirming the causal nature of AGK deficiency in Sengers syndrome. The loss of AGK led to a decrease of the adenine nucleotide translocator in the inner mitochondrial membrane in muscle, consistent with a role of AGK in driving the assembly of the translocator as a result of its effects on phospholipid metabolism in mitochondria.

DOI10.1016/j.ajhg.2011.12.005
Alternate JournalAm. J. Hum. Genet.
Citation Key10.1016/j.ajhg.2011.12.005
PubMed ID22284826
PubMed Central IDPMC3276657
Grant ListGGP11011 / / Telethon / Italy
GGP11139 / / Telethon / Italy
GPP10005 / / Telethon / Italy