TY - JOUR
T1 - Acute Infantile Liver Failure Due to Mutations in the TRMU Gene
AU - Zeharia, Avraham
AU - Shaag, Avraham
AU - Pappo, Orit
AU - Mager-Heckel, Anne Marie
AU - Saada, Ann
AU - Beinat, Marine
AU - Karicheva, Olga
AU - Mandel, Hanna
AU - Ofek, Noa
AU - Segel, Reeval
AU - Marom, Daphna
AU - Rötig, Agnes
AU - Tarassov, Ivan
AU - Elpeleg, Orly
N1 - Funding Information:
We are grateful to the patients and their families, to Mrs. Noa Cohen and Mrs. Corinne Belaiche for their dedicated assistance, to Prof. Shoshy Altuvia for fruitful discussions, to Prof. Michael Wilschanski for sharing of patient 1116 data, and to Dr. Israela Lerer and Prof. Elon Pras for provision of anonymous control samples. This work was supported in part by funding from the Joint Research Fund of the Hebrew University and Hadassah Medical Organization to N.O.; the Israel Science Foundation (1354-2005) to A.S and O.E; the Israeli Ministry of Health and Association Française contre les Myopathies to A.S, I.T., and O.K.; and the Fondation pour la Recherche Médicale and Agence Nationale de la Recherche Scientifique to I.T. and A.M.M.H.
PY - 2009/9/11
Y1 - 2009/9/11
N2 - Acute liver failure in infancy accompanied by lactic acidemia was previously shown to result from mtDNA depletion. We report on 13 unrelated infants who presented with acute liver failure and lactic acidemia with normal mtDNA content. Four died during the acute episodes, and the survivors never had a recurrence. The longest follow-up period was 14 years. Using homozygosity mapping, we identified mutations in the TRMU gene, which encodes a mitochondria-specific tRNA-modifying enzyme, tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase. Accordingly, the 2-thiouridylation levels of the mitochondrial tRNAs were markedly reduced. Given that sulfur is a TRMU substrate and its availability is limited during the neonatal period, we propose that there is a window of time whereby patients with TRMU mutations are at increased risk of developing liver failure.
AB - Acute liver failure in infancy accompanied by lactic acidemia was previously shown to result from mtDNA depletion. We report on 13 unrelated infants who presented with acute liver failure and lactic acidemia with normal mtDNA content. Four died during the acute episodes, and the survivors never had a recurrence. The longest follow-up period was 14 years. Using homozygosity mapping, we identified mutations in the TRMU gene, which encodes a mitochondria-specific tRNA-modifying enzyme, tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase. Accordingly, the 2-thiouridylation levels of the mitochondrial tRNAs were markedly reduced. Given that sulfur is a TRMU substrate and its availability is limited during the neonatal period, we propose that there is a window of time whereby patients with TRMU mutations are at increased risk of developing liver failure.
UR - http://www.scopus.com/inward/record.url?scp=69649100936&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2009.08.004
DO - 10.1016/j.ajhg.2009.08.004
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C2 - 19732863
AN - SCOPUS:69649100936
SN - 0002-9297
VL - 85
SP - 401
EP - 407
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -