A Novel Regulatory Defect in the Branched‐Chain α‐Keto Acid Dehydrogenase Complex Due to a Mutation in the PPM1K Gene Causes a Mild Variant Phenotype of Maple Syrup Urine Disease. Issue 2 (12th December 2012)

• Record Type: Journal Article
• Authors: Oyarzabal, Alfonso; Martínez‐Pardo, Mercedes; Merinero, Begoña; Navarrete, Rosa; Desviat, Lourdes R; Ugarte, Magdalena; Rodríguez‐Pombo, Pilar
• Is Part Of: Human mutation. Volume 34:Issue 2(2013:Feb.)
• Page Start: 355
• Page End: 362
• Publication Date: 2012-12-12
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22242
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="graphical" xml:lang="en" id="humu22242-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>We describe the unreported involvement of the cell‐survival and stress‐signaling essential mitochondrial phosphatase (PP2CM), a member of the branched‐chain α‐ketoacid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD). The disease‐causing mutation was identified in a patient with a mild variant phenotype. SNP array‐based genotyping showed a copy‐neutral homozygous pattern for chromosome 4. Mutation analysis of the candidate gene, <italic>PPM1K</italic>, revealed a homozygous c.417_418delTA change. The rescue of BCKDH activity upon transfection with wild‐type <italic>PPM1K</italic> verified the variant's involvement in clinical disease. <boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg1tt8nrb1" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>