Lack of the Mitochondrial Protein Acylglycerol Kinase Causes Sengers Syndrome

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• 作者：Johannes  ; A. Mayr¹ ; ⁹ ; Tobias  ; B. Haack² ; ³ ; ⁹ ; Elisabeth Graf² ; Franz  ; A. Zimmermann¹ ; Thomas Wieland² ; Birgit Haberberger² ; ³ ; Andrea Superti-Furga⁴ ; ¹⁰ ; Janbernd Kirschner⁴ ; Beat Steinmann⁵ ; Matthias  ; R. Baumgartner⁵ ; Isabella Moroni⁶ ; Eleonora Lamantea⁶ ; Massimo Zeviani⁶ ; Richard  ; J. Rodenburg⁷ ; Jan Smeitink⁷ ; Tim  ; M. Strom² ; ³ ; Thomas Meitinger² ; ³ ; ⁸ ; Wolfgang Sperl¹ ; Holger Prokisch² ; ³ ; ^{prokisch@helmholtz-muenchen.de}
• 刊名：The American Journal of Human Genetics
• 出版年：2012
• 出版时间：10 February 2012
• 年：2012
• 卷：90
• 期：2
• 页码：314-320
• 全文大小：444 K

文摘

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.