Acute Infantile Liver Failure Due to Mutations in the TRMU Gene

Slides:

Advertisements

Similar presentations

Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and.

Advertisements

Deletions of the INK4A Gene Occur in Malignant Peripheral Nerve Sheath Tumors but not in Neurofibromas Helen P. Kourea, Irene Orlow, Bernd W. Scheithauer,

Transient Infantile Hypertriglyceridemia, Fatty Liver, and Hepatic Fibrosis Caused by Mutated GPD1, Encoding Glycerol-3-Phosphate Dehydrogenase 1 Lina.

One-Step Ligation on RNA Amplification for the Detection of Point Mutations Lei Zhang, Jingjing Wang, Mia Coetzer, Stephanie Angione, Rami Kantor, Anubhav.

Cosuppression in Drosophila: Gene Silencing of Alcohol dehydrogenase by white-Adh Transgenes Is Polycomb Dependent Manika Pal-Bhadra, Utpal Bhadra, James.

A Novel Cofactor for p300 that Regulates the p53 Response

Activation of the Erythropoietin Receptor Is Not Required for Internalization of Bound Erythropoietin by Diana L. Beckman, Lilie L. Lin, Mary E. Quinones,

Skin-Specific Expression of ank-393, a Novel Ankyrin-3 Splice Variant

Mutation Spectrum of the Survival of Motor Neuron 1 and Functional Analysis of Variants in Chinese Spinal Muscular Atrophy Yu-jin Qu, Jin-li Bai, Yan-yan.

Matrix Metalloproteinase 9 Expression is Coordinately Modulated by the KRE-M9 and 12-O-Tetradecanoyl-Phorbol-13-Acetate Responsive Elements Takashi Kobayashi,

Loss-of-Function Mutations in LRRC6, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms, Cause Primary Ciliary Dyskinesia Esther.

Volume 116, Issue 2, Pages (February 1999)

Expression of Type XVI Collagen in Human Skin Fibroblasts: Enhanced Expression in Fibrotic Skin Diseases Atsushi Akagi, Shingo Tajima, Yutaka Nagai

Volume 26, Issue 5, Pages (June 2007)

Undifferentiated Small Round Cell Sarcomas with Rare EWS Gene Fusions

GRACILE Syndrome, a Lethal Metabolic Disorder with Iron Overload, Is Caused by a Point Mutation in BCS1L Ilona Visapää, Vineta Fellman, Jouni Vesa, Ayan.

Functional Consequences of PRODH Missense Mutations

Mutations of the Mitochondrial-tRNA Modifier MTO1 Cause Hypertrophic Cardiomyopathy and Lactic Acidosis Daniele Ghezzi, Enrico Baruffini, Tobias B. Haack,

Rose-Anne Romano, Barbara Birkaya, Satrajit Sinha

TAT-mediated Delivery of LAD Restores Pyruvate Dehydrogenase Complex Activity in the Mitochondria of Patients with LAD Deficiency Matan Rapoport, Ann.

Antisense Masking of an hnRNP A1/A2 Intronic Splicing Silencer Corrects SMN2 Splicing in Transgenic Mice Yimin Hua, Timothy A. Vickers, Hazeem L. Okunola,

Mutations in PADI6 Cause Female Infertility Characterized by Early Embryonic Arrest Yao Xu, Yingli Shi, Jing Fu, Min Yu, Ruizhi Feng, Qing Sang, Bo Liang,

In situ localization and quantification of seventy-two – kilodalton type IV collagenase in aneurysmal, occlusive, and normal aorta William D. McMillan,

Sequence Analysis and Homology Modeling Suggest That Primary Congenital Glaucoma on 2p21 Results from Mutations Disrupting Either the Hinge Region or.

Volume 25, Issue 6, Pages (June 2017)

Mutations of the SYCP3 Gene in Women with Recurrent Pregnancy Loss

Communication with the Exon-Junction Complex and Activation of Nonsense-Mediated Decay by Human Upf Proteins Occur in the Cytoplasm Guramrit Singh, Steffen.

Volume 117, Issue 3, Pages (September 1999)

Volume 22, Issue 2, Pages (February 2014)

Volume 18, Issue 1, Pages (January 2011)

Molecular Monitoring of Chronic Myelogenous Leukemia

An RMND1 Mutation Causes Encephalopathy Associated with Multiple Oxidative Phosphorylation Complex Deficiencies and a Mitochondrial Translation Defect

Hung-Chun Yu, Jennifer L

Markus Zettl, Michael Way Current Biology

H. Randolph Byers, Mina Yaar, Mark S. Eller, Nicole L

Olga M. Mazina, Marjorie A. Phillips, Trevor Williams, Carol A

TFIIH Subunit Alterations Causing Xeroderma Pigmentosum and Trichothiodystrophy Specifically Disturb Several Steps during Transcription Amita Singh,

ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy Tobias B. Haack, Robert Kopajtich, Peter Freisinger,

Volume 22, Issue 12, Pages (December 2014)

Molecular Therapy - Nucleic Acids

Mutations in C12orf65 in Patients with Encephalomyopathy and a Mitochondrial Translation Defect Hana Antonicka, Elsebet Østergaard, Florin Sasarman,

Sex-Linked period Genes in the Silkmoth, Antheraea pernyi

Codependent Activators Direct Myoblast-Specific MyoD Transcription

Volume 90, Issue 4, Pages (August 1997)

An mtDNA Mutation in the Initiation Codon of the Cytochrome C Oxidase Subunit II Gene Results in Lower Levels of the Protein and a Mitochondrial Encephalomyopathy

Increased Expression of Wnt2 and SFRP4 in Tsk Mouse Skin: Role of Wnt Signaling in Altered Dermal Fibrillin Deposition and Systemic Sclerosis Julie Bayle,

PEX3 Is the Causal Gene Responsible for Peroxisome Membrane Assembly–Defective Zellweger Syndrome of Complementation Group G Kamran Ghaedi, Masanori.

Analyses of the Effects That Disease-Causing Missense Mutations Have on the Structure and Function of the Winged-Helix Protein FOXC1 Ramsey A. Saleem,

The Scaffold Protein Atg11 Recruits Fission Machinery to Drive Selective Mitochondria Degradation by Autophagy Kai Mao, Ke Wang, Xu Liu, Daniel J. Klionsky

Volume 17, Issue 3, Pages (March 2013)

Autosomal-Dominant Striatal Degeneration Is Caused by a Mutation in the Phosphodiesterase 8B Gene Silke Appenzeller, Anja Schirmacher, Hartmut Halfter,

Ribosomal Protein L5 and L11 Mutations Are Associated with Cleft Palate and Abnormal Thumbs in Diamond-Blackfan Anemia Patients Hanna T. Gazda, Mee Rie.

Transcriptional Control of SLC26A4 Is Involved in Pendred Syndrome and Nonsyndromic Enlargement of Vestibular Aqueduct (DFNB4) Tao Yang, Hilmar Vidarsson,

Volume 15, Issue 6, Pages (June 2007)

Volume 57, Issue 6, Pages (June 2000)

Defining the Regulatory Elements in the Proximal Promoter of ΔNp63 in Keratinocytes: Potential Roles for Sp1/Sp3, NF-Y, and p63 Rose-Anne Romano, Barbara.

Structure of the Siz/PIAS SUMO E3 Ligase Siz1 and Determinants Required for SUMO Modification of PCNA Ali A. Yunus, Christopher D. Lima Molecular Cell

Exome Sequencing Identifies CCDC8 Mutations in 3-M Syndrome, Suggesting that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human Growth

George Simos, Anke Sauer, Franco Fasiolo, Eduard C Hurt Molecular Cell

Identification and Characterization of a Mutation, in the Human UDP-Galactose-4- Epimerase Gene, Associated with Generalized Epimerase-Deficiency Galactosemia

Loss of SUFU Function in Familial Multiple Meningioma

Exocrine Pancreatic Insufficiency, Dyserythropoeitic Anemia, and Calvarial Hyperostosis Are Caused by a Mutation in the COX4I2 Gene Eyal Shteyer, Ann.

Transcriptional Termination Factors for RNA Polymerase II in Yeast

Ricksen S. Winardhi, Qingnan Tang, Jin Chen, Mingxi Yao, Jie Yan

Exon Skipping in IVD RNA Processing in Isovaleric Acidemia Caused by Point Mutations in the Coding Region of the IVD Gene Jerry Vockley, Peter K. Rogan,

Mutations in the Fatty Acid 2-Hydroxylase Gene Are Associated with Leukodystrophy with Spastic Paraparesis and Dystonia Simon Edvardson, Hiroko Hama,

Volume 26, Issue 5, Pages (June 2007)

Bradford Coffee, Fuping Zhang, Stephanie Ceman, Stephen T

Heterozygous RNF13 Gain-of-Function Variants Are Associated with Congenital Microcephaly, Epileptic Encephalopathy, Blindness, and Failure to Thrive

Mutations in the Mitochondrial Seryl-tRNA Synthetase Cause Hyperuricemia, Pulmonary Hypertension, Renal Failure in Infancy and Alkalosis, HUPRA Syndrome

Presentation transcript:

Acute Infantile Liver Failure Due to Mutations in the TRMU Gene Avraham Zeharia, Avraham Shaag, Orit Pappo, Anne-Marie Mager-Heckel, Ann Saada, Marine Beinat, Olga Karicheva, Hanna Mandel, Noa Ofek, Reeval Segel, Daphna Marom, Agnes Rötig, Ivan Tarassov, Orly Elpeleg The American Journal of Human Genetics Volume 85, Issue 3, Pages 401-407 (September 2009) DOI: 10.1016/j.ajhg.2009.08.004 Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 1 Histopathological Findings in Liver Tissue (A) Liver tissue showing marked oncocytic change in the hepatocytes (arrow) and focal ballooning degeneration of hepatocytes (arrowhead) (H&E). (B) Hepatic tissue with markedly disrupted architecture characterized by nodule formation with prominent sinusoidal fibrosis (Masson Trichrome stain). The American Journal of Human Genetics 2009 85, 401-407DOI: (10.1016/j.ajhg.2009.08.004) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 2 Analysis of Mitochondrial Translation in the Patients' Fibroblasts The mitochondrial translation products on SDS-PAAG are indicated according to a standard pattern.7 Assays were performed in the fibroblasts of a control (lane 1) and three patients (lanes 2–4 for patients 2624, 2859, and 1910, respectively). The relative values were normalized to tubulin (panel below the autoradiographs) and are presented as a diagram. Error bars represent the results of two independent experiments. The American Journal of Human Genetics 2009 85, 401-407DOI: (10.1016/j.ajhg.2009.08.004) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 3 The Mutations Identified in the TRMU Gene The mutations identified in the TRMU gene of patients with acute liver failure, depicted on a schematic representation of the conserved domains (NCBI conserved domains website). G14 is one of six residues (red arrowheads) that form the P loop motif (SGGXDS), which is an ATP-binding motif commonly found in enzymes responsible for RNA modifications.14 The American Journal of Human Genetics 2009 85, 401-407DOI: (10.1016/j.ajhg.2009.08.004) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 4 Thio-Modification in Mitochondrial tRNAs Analysis of thio-modification at position 2 of the wobble uridine via RNA hybridization of mitochondrial (mt-tRNA-Lys, mt-tRNA-Glu, and mt-tRNA-Gln) and cytoplasmic (cy-tRNA-Lys) tRNAs separated in APM-containing gels (+APM, upper panel). For quantification, the same amount of RNA obtained from patient and control fibroblasts was separated in gels without APM (-APM, middle panel). The retarded diffused zones correspond to the thiolated and nonthiolated versions of each tRNA (Thiolated and Nonthiolated, respectively). The hybridization probes and the numbers of the RNA samples are indicated at the top of the autoradiographs; the numbers correspond to the samples described under the diagram at the bottom. The quantification of the modification is presented at the bottom panel and is expressed as a percentage of the thiolated signal from the thiolated + nonthiolated signals (as presented in the -APM gel at the middle panel), normalized against the control fibroblasts. The deviations are indicated as a result of two to three independent measures (for the control fibroblasts, the deviation was quasi null and is therefore not indicated). The American Journal of Human Genetics 2009 85, 401-407DOI: (10.1016/j.ajhg.2009.08.004) Copyright © 2009 The American Society of Human Genetics Terms and Conditions

Figure 5 Quantification of Mitochondrial tRNAs by RNA Hybridization RNA was isolated from the fibroblasts of a control (1) and three patients (2–4 for patients 2624, 2859, and 1910, respectively). Relative values normalized to the 5S rRNA signal are presented in the diagram below the autoradiographs (the various tRNAs are indicated on the x axis only by their respective amino acid abbreviation; thus, Leu stands for mitochondrial tRNA-Leu transcript). Average values of two to three independent experiments are presented. The error was never higher than 10%. The American Journal of Human Genetics 2009 85, 401-407DOI: (10.1016/j.ajhg.2009.08.004) Copyright © 2009 The American Society of Human Genetics Terms and Conditions