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

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,

Stephen Lory, PhD, Jeffrey K. Ichikawa, PhD CHEST

Arterioscler Thromb Vasc Biol

Molecular Diagnostics in Preimplantation Genetic Diagnosis

Homozygous Defects in LMNA, Encoding Lamin A/C Nuclear-Envelope Proteins, Cause Autosomal Recessive Axonal Neuropathy in Human (Charcot-Marie-Tooth Disorder.

Naomi J. Lohr, Jean P. Molleston, Kevin A

CLPB Variants Associated with Autosomal-Recessive Mitochondrial Disorder with Cataract, Neutropenia, Epilepsy, and Methylglutaconic Aciduria Carol Saunders,

The H Syndrome Is Caused by Mutations in the Nucleoside Transporter hENT3 Vered Molho-Pessach, Israela Lerer, Dvorah Abeliovich, Ziad Agha, Abdulasalam.

Isothermal Multiple Displacement Amplification

Deficiency of the ADP-Forming Succinyl-CoA Synthase Activity Is Associated with Encephalomyopathy and Mitochondrial DNA Depletion Orly Elpeleg, Chaya.

A Missense Mutation (R565W) in Cirhin (FLJ14728) in North American Indian Childhood Cirrhosis Pierre Chagnon, Jacques Michaud, Grant Mitchell, Jocelyne.

Development and Applications of a BRAF Oligonucleotide Microarray

RNAi Related Mechanisms Affect Both Transcriptional and Posttranscriptional Transgene Silencing in Drosophila Manika Pal-Bhadra, Utpal Bhadra, James.

Sherif Abou Elela, Haller Igel, Manuel Ares Cell

Mutations in the Human Sterol Δ7-Reductase Gene at 11q12-13 Cause Smith-Lemli- Opitz Syndrome Christopher A. Wassif, Cheryl Maslen, Stivelia Kachilele-Linjewile,

J. Catalán, K. Autio, E. Kuosma, H. Norppa

Differential HFE allele expression in hemochromatosis heterozygotes

Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss Yun Li, Esther Pohl, Redouane Boulouiz, Margit Schraders,

Quantitative Analysis of Survival Motor Neuron Copies: Identification of Subtle SMN1 Mutations in Patients with Spinal Muscular Atrophy, Genotype-Phenotype.

William A. Paznekas, Michael L. Cunningham, Timothy D. Howard, Bruce R

Clustered 11q23 and 22q11 Breakpoints and 3:1 Meiotic Malsegregation in Multiple Unrelated t(11;22) Families Tamim H. Shaikh, Marcia L. Budarf, Livija.

A Novel Alu-Like Element Rearranged in the Dystrophin Gene Causes a Splicing Mutation in a Family with X-Linked Dilated Cardiomyopathy Alessandra Ferlini,

Reliable Identification of Genomic Variants from RNA-Seq Data

Toward a Survey of Somatic Mutation of the NF1 Gene in Benign Neurofibromas of Patients with Neurofibromatosis Type 1 Ingrid Eisenbarth, Kim Beyer, Winfrid.

CLPB Variants Associated with Autosomal-Recessive Mitochondrial Disorder with Cataract, Neutropenia, Epilepsy, and Methylglutaconic Aciduria Carol Saunders,

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,

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

The mRNA for Protease Nexin-1 is Expressed in Human Dermal Papilla Cells and its Level is Affected by Androgen Tadashige Sonoda, Yuji Asada, Sotaro Kurata,

A Novel Mouse Gene, Sh3yl1, is Expressed in the Anagen Hair Follicle

Acute Infantile Liver Failure Due to Mutations in the TRMU Gene

Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3 Tarja Joensuu, Riikka Hämäläinen, Bo Yuan, Cheryl Johnson, Saara.

Peter Ianakiev, Michael W

Capillary Malformation–Arteriovenous Malformation, a New Clinical and Genetic Disorder Caused by RASA1 Mutations Iiro Eerola, Laurence M. Boon, John.

Expression Profiles of Tyrosine Kinases in Cultured Follicular Papilla Cells Versus Dermal Fibroblasts Dawen Yu, Qiong Cao, Zhijun He, Tung-Tien Sun

Molecular Diagnostics in Preimplantation Genetic Diagnosis

PSMB8 Encoding the β5i Proteasome Subunit Is Mutated in Joint Contractures, Muscle Atrophy, Microcytic Anemia, and Panniculitis-Induced Lipodystrophy.

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene Daniel.

Kimberly C. Sippel, Rebecca E. Fraioli, Gary D. Smith, Mary E

Linear Mitochondrial Plasmids of F

Joubert Syndrome 2 (JBTS2) in Ashkenazi Jews Is Associated with a TMEM216 Mutation Simon Edvardson, Avraham Shaag, Shamir Zenvirt, Yaniv Erlich, Gregory.

A Heterozygous Truncating Mutation in RRM2B Causes Autosomal-Dominant Progressive External Ophthalmoplegia with Multiple mtDNA Deletions Henna Tyynismaa,

Mutations of the Ephrin-B1 Gene Cause Craniofrontonasal Syndrome

Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome

Biallelic Mutations in PATL2 Cause Female Infertility Characterized by Oocyte Maturation Arrest Biaobang Chen, Zhihua Zhang, Xiaoxi Sun, Yanping Kuang,

E.J. Hollox, J.A.L. Armour, J.C.K. Barber

Lethal Contractural Syndrome Type 3 (LCCS3) Is Caused by a Mutation in PIP5K1C, Which Encodes PIPKIγ of the Phophatidylinsitol Pathway Ginat Narkis,

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

Jeremy E. Wilusz, Susan M. Freier, David L. Spector Cell

The Gene Mutated in Variant Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN6) and in nclf Mutant Mice Encodes a Novel Predicted Transmembrane Protein

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

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene Daniel.

A Deleterious Mutation in SAMD9 Causes Normophosphatemic Familial Tumoral Calcinosis Orit Topaz, Margarita Indelman, Ilana Chefetz, Dan Geiger, Aryeh.

David A. Norris, Brian L. Kotzin Journal of Investigative Dermatology

Mutations in CHEK2 Associated with Prostate Cancer Risk

Bart A. Jessen, Marjorie A. Phillips, Robert H. Rice

Mutations in PRPS1, Which Encodes the Phosphoribosyl Pyrophosphate Synthetase Enzyme Critical for Nucleotide Biosynthesis, Cause Hereditary Peripheral.

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

Akio Tanaka, Sarah Weinel, Nikoletta Nagy, Mark O'Driscoll, Joey E

Meconium Ileus Caused by Mutations in GUCY2C, Encoding the CFTR-Activating Guanylate Cyclase 2C Hila Romi, Idan Cohen, Daniella Landau, Suliman Alkrinawi,

Polymorphic X-Chromosome Inactivation of the Human TIMP1 Gene

Kit-Sing Au, Adelaide A. Hebert, E. Steve Roach, Hope Northrup

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

Quantitative Analysis of Survival Motor Neuron Copies: Identification of Subtle SMN1 Mutations in Patients with Spinal Muscular Atrophy, Genotype-Phenotype.

A Mutation in LIPN, Encoding Epidermal Lipase N, Causes a Late-Onset Form of Autosomal-Recessive Congenital Ichthyosis Shirli Israeli, Ziyad Khamaysi,

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,

Darryl Y. Nishimura, Ruth E. Swiderski, Charles C. Searby, Erik M

Zuoheng Wang, Mary Sara McPeek The American Journal of Human Genetics

Identification of a New Splice Form of the EDA1 Gene Permits Detection of Nearly All X- Linked Hypohidrotic Ectodermal Dysplasia Mutations Alex W. Monreal,

K. Miura, M. Obama, K. Yun, H. Masuzaki, Y. Ikeda, S. Yoshimura, T

Presentation transcript:

Mutations in the Mitochondrial Seryl-tRNA Synthetase Cause Hyperuricemia, Pulmonary Hypertension, Renal Failure in Infancy and Alkalosis, HUPRA Syndrome Ruth Belostotsky, Efrat Ben-Shalom, Choni Rinat, Rachel Becker-Cohen, Sofia Feinstein, Sharon Zeligson, Reeval Segel, Orly Elpeleg, Suheir Nassar, Yaacov Frishberg The American Journal of Human Genetics Volume 88, Issue 2, Pages 193-200 (February 2011) DOI: 10.1016/j.ajhg.2010.12.010 Copyright © 2011 The American Society of Human Genetics Terms and Conditions

Figure 1 Implementation of SNP Microarray Analysis for the Identification of Mutation in SARS2 (A) Pedigrees of the families. DNA samples from individuals marked with asterisk were analyzed for the c.1169A>G mutation in SARS2. (B) Homozygosity mapping of DNA derived from patients F1:III-1 and F1:III-6. Detection of a common homozygous region on chromosome 19 by Genotyping Console (left) and KinSNP (right) software. SARS2 is located at the very end of the shared fragment. The American Journal of Human Genetics 2011 88, 193-200DOI: (10.1016/j.ajhg.2010.12.010) Copyright © 2011 The American Society of Human Genetics Terms and Conditions

Figure 2 Electron Micrograph of Renal Tissue Obtained from Patient F1:III-1 Abnormal enlarged mitochondria with paracrystalline inclusions in a portion of the tubular epithelial cells (red arrows). Normal mitochondrion is marked in a blue arrow. The American Journal of Human Genetics 2011 88, 193-200DOI: (10.1016/j.ajhg.2010.12.010) Copyright © 2011 The American Society of Human Genetics Terms and Conditions

Figure 3 Mutation Analysis of DNA Samples from Patients, Carriers, and Normal Individual and Confirmation of the Conservation among Species of the Mutated Amino Acid in SARS2 (A) DNA sequence identifying the c.1169A>G mutation in SARS2. (B) Restriction enzyme analysis with BsaJI: this mutation introduces a restriction site for this enzyme, which results in the digestion of the 166 bp oligonucleotide into 94 bp and 72 bp fragments. (C) Multiple sequence alignment of SARS2 in various species with ClustalW program. In red: the amino acid corresponding to the mutation in human DNA c.1169A>G (p.Asp390Gly). The American Journal of Human Genetics 2011 88, 193-200DOI: (10.1016/j.ajhg.2010.12.010) Copyright © 2011 The American Society of Human Genetics Terms and Conditions

Figure 4 Comparison of the Secondary Structures of E. coli tRNASer with Two Human Mitochondrial tRNAsSer Human tRNASerAGY (A) and tRNASerUCN (B) are shown. The American Journal of Human Genetics 2011 88, 193-200DOI: (10.1016/j.ajhg.2010.12.010) Copyright © 2011 The American Society of Human Genetics Terms and Conditions

Figure 5 Quantitative Analysis of tRNASerAGY and tRNASerUCN Amino Acylation in EBV-Transformed Lymphocyte Cultures (A) Northern blot: equal amounts (2 μg) of total RNA purified from normal and patient-derived lymphocyte lines were separated at 4°C on an acidic 6.5% polyacrylamide-7 M urea gel. Hybridization with 32P-labeled probes for tRNASerAGY and tRNASerUCN. The blots were then stripped and rehybridized with probes for MT-tRNALeu. One representative northern hybridization, out of three experiments, is presented. DA denotes deacylated tRNA. (B) Histogram presentation of the data from (A). The intensity of hybridization signals was normalized by the signal of loading control MT-tRNALeu and is presented as percentage of the signal of the corresponding probe in the control. The American Journal of Human Genetics 2011 88, 193-200DOI: (10.1016/j.ajhg.2010.12.010) Copyright © 2011 The American Society of Human Genetics Terms and Conditions