Acute Infantile Liver Failure Due to Mutations in the TRMU Gene

被引：171

作者：

Zeharia, Avraham ^{[1
,4
,5
,6
]}

Shaag, Avraham ^{[1
]}

Pappo, Orit ^{[2
]}

Mager-Heckel, Anne-Marie ^{[7
]}

Saada, Ann ^{[1
]}

Beinat, Marine ^{[8
,9
]}

Karicheva, Olga ^{[7
]}

Mandel, Hanna ^{[10
]}

Ofek, Noa ^{[3
]}

Segel, Reeval ^{[11
]}

Marom, Daphna ^{[4
,5
,6
]}

Roetig, Agnes ^{[8
,9
]}

Tarassovs, Ivan ^{[7
]}

Elpeleg, Orly ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Med Ctr, Dept Human Genet & Metab Dis, Jerusalem, Israel

[2] Hebrew Univ Jerusalem, Med Ctr, Dept Pathol, Jerusalem, Israel

[3] Hebrew Univ Jerusalem, Med Ctr, Dept Neonatol, Jerusalem, Israel

[4] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[5] Tel Aviv Univ, Day Hospitalizat Unit, Tel Aviv, Israel

[6] Tel Aviv Univ, Dept Pediat A, Schneider Childrens Med Ctr, Tel Aviv, Israel

[7] Univ Strasbourg, CNRS, UMR 7156, Strasbourg, France

[8] Univ Paris 05, Hop Necker Enfants Malad, INSERM, U781, F-75015 Paris, France

[9] Univ Paris 05, Hop Necker Enfants Malad, Dept Genet, F-75015 Paris, France

[10] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel

[11] Shaare Zedek Med Ctr, Inst Med Genet, Jerusalem, Israel

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2009年 / 85卷 / 03期

基金：

以色列科学基金会;

关键词：

MITOCHONDRIAL-DNA DEPLETION; CULTURED HUMAN-CELLS; TRANSFER-RNA; 1ST YEAR; BINDING; PROTEIN; LIFE;

D O I：

10.1016/j.ajhg.2009.08.004

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：401 / 407

页数：7

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