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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
XAMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder
Cell, Volume 154, No. 3, Year 2013
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Description
Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acid synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenosine and guanine nucleotides. We describe a distinct early-onset neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH) due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a potentially treatable early-onset neurodegenerative disease. © 2013 Elsevier Inc.
Authors & Co-Authors
Akizu, Naiara
United States, La Jolla
University of California, San Diego
Cantagrel, Vincent
United States, La Jolla
University of California, San Diego
France, Paris
Hôpital Necker Enfants Malades
Schroth, Jana
United States, La Jolla
University of California, San Diego
Cai, Na
United States, La Jolla
University of California, San Diego
Vaux, Keith K.
United States, La Jolla
University of California, San Diego
McCloskey, Douglas
United States, La Jolla
Department of Bioengineering
Naviaux, Robert K.
United States, La Jolla
University of California, San Diego
Van Vleet, Jeremy
United States, La Jolla
University of California, San Diego
Fenstermaker, Ali G.
United States, La Jolla
University of California, San Diego
Silhavy, Jennifer L.
United States, La Jolla
University of California, San Diego
Scheliga, Judith S.
United States, San Diego
Sanford Burnham Prebys Medical Discovery Institute
Toyama, Keiko
Japan, Suita
Osaka University
Morisaki, Hiroko
Japan, Suita
Osaka University
Sonmez, Fatma Mujgan
Turkey, Ankara
Turgut Özal Üniversitesi
Celep, Figen
Turkey, Trabzon
Karadeniz Technical University
Oraby, Azza M.
Egypt, Cairo
Faculty of Medicine
Zaki, Maha S.
Egypt, Giza
National Research Centre
Al-Baradie, Raidah Saleem
Saudi Arabia, Dammam
King Fahd Specialist Hospital
Faqeih, Eissa Ali
Saudi Arabia, Riyadh
King Fahad Medical City
Saleh, Mohammed Ali M.
Saudi Arabia, Riyadh
King Fahad Medical City
Spencer, Emily G.
United States, La Jolla
University of California, San Diego
Rosti, Rasim Özgür
United States, La Jolla
University of California, San Diego
Scott, Eric M.
United States, La Jolla
University of California, San Diego
Nickerson, Elizabeth
United States, Cambridge
Broad Institute
Gabriel, Stacey Bolk
United States, Cambridge
Broad Institute
Morisaki, Takayuki
Japan, Suita
Osaka University
Holmes, Edward W.
United States, San Diego
Sanford Consortium for Regenerative Medicine
Gleeson, Joseph G.
United States, La Jolla
University of California, San Diego
Statistics
Citations: 94
Authors: 28
Affiliations: 13
Identifiers
Doi:
10.1016/j.cell.2013.07.005
ISSN:
00928674
e-ISSN:
10974172
Research Areas
Genetics And Genomics