Phosphoserine Aminotransferase Deficiency: A Novel Disorder of the Serine Biosynthesis Pathway Claire E. Hart, Valerie Race, Younes Achouri, Elsa Wiame,

Slides:

Advertisements

Similar presentations

Functional Analysis of the Neurofibromatosis Type 2 Protein by Means of Disease- Causing Point Mutations Renee P. Stokowski, David R. Cox The American.

Advertisements

Detection of Exon 12 Mutations in the JAK2 Gene

Diagnostic Testing for Rett Syndrome by DHPLC and Direct Sequencing Analysis of the MECP2 Gene: Identification of Several Novel Mutations and Polymorphisms

Protein-Truncation Mutations in the RP2 Gene in a North American Cohort of Families with X-Linked Retinitis Pigmentosa Alan J. Mears, Linn Gieser, Denise.

Novel Mutations on EGFR Leu792 Potentially Correlate to Acquired Resistance to Osimertinib in Advanced NSCLC Kai Chen, MD, Fei Zhou, MD, Wenxiang Shen,

A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.

Wanlong Ma, Hagop Kantarjian, Xi Zhang, Chen-Hsiung Yeh, Zhong J

Identification of a Frameshift Mutation in Osterix in a Patient with Recessive Osteogenesis Imperfecta Pablo Lapunzina, Mona Aglan, Samia Temtamy, José.

Analysis of the COL1A1 and COL1A2 Genes by PCR Amplification and Scanning by Conformation-Sensitive Gel Electrophoresis Identifies Only COL1A1 Mutations.

Human Diallelic Insertion/Deletion Polymorphisms

Energetic Pathway Sampling in a Protein Interaction Domain

H-NS2 protein interacts with Lon and H-NS protein in vitro.

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

DNA Diagnostics by Surface-Bound Melt-Curve Reactions

Cloning of Dimethylglycine Dehydrogenase and a New Human Inborn Error of Metabolism, Dimethylglycine Dehydrogenase Deficiency Barbara A. Binzak, Ron.

Volume 70, Issue 1, Pages (July 2006)

Functional Consequences of PRODH Missense Mutations

Mutations in ZDHHC9, Which Encodes a Palmitoyltransferase of NRAS and HRAS, Cause X-Linked Mental Retardation Associated with a Marfanoid Habitus F.

Factor H Mutations in Hemolytic Uremic Syndrome Cluster in Exons 18–20, a Domain Important for Host Cell Recognition Anna Richards, Mark R. Buddles,

Detection of Exon 12 Mutations in the JAK2 Gene

Epstein–Barr virus BZLF1 gene polymorphisms: malignancy related or geographically distributed variants? M.A. Lorenzetti, M. Gantuz, J. Altcheh, E. De.

Identification of Novel Missense Mutations of Cardiac Ryanodine Receptor Gene in Exercise-Induced Sudden Death at Autopsy Wendy Creighton, Renu Virmani,

Peter Ianakiev, Michael W

Splice Site and Deletion Mutations in Keratin (KRT1 and KRT10) Genes: Unusual Phenotypic Alterations in Scandinavian Patients with Epidermolytic Hyperkeratosis

Volume 60, Issue 5, Pages (November 2001)

A Mutation in the Fibroblast Growth Factor 14 Gene Is Associated with Autosomal Dominant Cerebral Ataxia John C. van Swieten, Esther Brusse, Bianca M.

Homo-Oligomerization of Human Corneodesmosin Is Mediated by Its N-Terminal Glycine Loop Domain Cécile Caubet, Nathalie Jonca, Frédéric Lopez, Jean-Pierre.

Volume 64, Issue 5, Pages (November 2003)

Mutational analysis of TOX3 in Chinese Han women with polycystic ovary syndrome Yuqian Cui, Shigang Zhao, Han Zhao, Yue Lv, Mengru Yu, Yu Wang, Zi-Jiang.

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

Mutations in the Sepiapterin Reductase Gene Cause a Novel Tetrahydrobiopterin- Dependent Monoamine-Neurotransmitter Deficiency without Hyperphenylalaninemia

A Nonsense Mutation in CRYBB1 Associated with Autosomal Dominant Cataract Linked to Human Chromosome 22q Donna S. Mackay, Olivera B. Boskovska, Harry.

A Presenilin-1 Truncating Mutation Is Present in Two Cases with Autopsy-Confirmed Early-Onset Alzheimer Disease Carolyn Tysoe, Joanne Whittaker, John.

Fabry Disease: Novel α-Galactosidase A 3′-Terminal Mutations Result in Multiple Transcripts Due to Aberrant 3′-End Formation Makiko Yasuda, Junaid Shabbeer,

Guofang Hu, Meltem Önder, Melissa Gill, Burhan Aksakal, Murat Öztas, M

A Novel Method for Creating Artificial Mutant Samples for Performance Evaluation and Quality Control in Clinical Molecular Genetics Michael Jarvis, Ramaswamy.

Sadaf Naz, Chantal M. Giguere, David C. Kohrman, Kristina L

Autosomal-Dominant Woolly Hair Resulting from Disruption of Keratin 74 (KRT74), a Potential Determinant of Human Hair Texture Yutaka Shimomura, Muhammad.

Mutations in ZDHHC9, Which Encodes a Palmitoyltransferase of NRAS and HRAS, Cause X-Linked Mental Retardation Associated with a Marfanoid Habitus F.

Volume 63, Issue 4, Pages (April 2003)

Characterization of a Germline Mosaicism in Families with Lowe Syndrome, and Identification of Seven Novel Mutations in the OCRL1 Gene Véronique Satre,

Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta Figen Seymen, Youn Jung Kim, Ye Ji Lee,

Ryan McDaniell, Daniel M. Warthen, Pedro A

Deletion of PREPL, a Gene Encoding a Putative Serine Oligopeptidase, in Patients with Hypotonia-Cystinuria Syndrome Jaak Jaeken, Kevin Martens, Inge.

Maternal Transmission of the 3 bp Deletion within Exon 7 of the STS Gene in Steroid Sulfatase Deficiency Margarita Valdes-Flores Journal of Investigative.

X-Linked Dominant Scapuloperoneal Myopathy Is Due to a Mutation in the Gene Encoding Four-and-a-Half-LIM Protein 1 Catarina M. Quinzii, Tuan H. Vu, K.

Structure of the BRCT Repeats of BRCA1 Bound to a BACH1 Phosphopeptide

Characterization and Mutation Analysis of Human LEFTY A and LEFTY B, Homologues of Murine Genes Implicated in Left-Right Axis Development K. Kosaki,

Assessing the Functional Characteristics of Synonymous and Nonsynonymous Mutation Candidates by Use of Large DNA Constructs A.M. Eeds, D. Mortlock, R.

Mutations Disrupting Selenocysteine Formation Cause Progressive Cerebello-Cerebral Atrophy Orly Agamy, Bruria Ben Zeev, Dorit Lev, Barak Marcus, Dina.

Maple Syrup Urine Disease: Identification and Carrier-Frequency Determination of a Novel Founder Mutation in the Ashkenazi Jewish Population Lisa Edelmann,

Bruce L. Zuraw, MD, Jack Herschbach, BA

KIT Gene Deletions at the Intron 10−Exon 11 Boundary in GI Stromal Tumors Christopher L. Corless, Laura McGreevey, Ajia Town, Arin Schroeder, Troy Bainbridge,

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

Volume 15, Issue 6, Pages (June 2007)

Molecular Therapy - Methods & Clinical Development

Early Death from Cardiomyopathy in a Family with Autosomal Dominant Striate Palmoplantar Keratoderma and Woolly Hair Associated with a Novel Insertion.

Anthony M. Raizis, Martin M. Ferguson, David T. Nicholls, Derek W

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

SUR-8, a Conserved Ras-Binding Protein with Leucine-Rich Repeats, Positively Regulates Ras-Mediated Signaling in C. elegans Derek S Sieburth, Qun Sun,

Arun Kumar, Satish C. Girimaji, Mahesh R. Duvvari, Susan H. Blanton

Mark S. Dunstan, Debraj GuhaThakurta, David. E. Draper, Graeme L. Conn

Two Exon-Skipping Mutations as the Molecular Basis of Succinic Semialdehyde Dehydrogenase Deficiency (4-Hydroxybutyric Aciduria) Ken L. Chambliss, Debra.

Mutations in the DLG3 Gene Cause Nonsyndromic X-Linked Mental Retardation Patrick Tarpey, Josep Parnau, Matthew Blow, Hayley Woffendin, Graham Bignell,

Cloning of Dimethylglycine Dehydrogenase and a New Human Inborn Error of Metabolism, Dimethylglycine Dehydrogenase Deficiency Barbara A. Binzak, Ron.

Alexandre Irrthum, Marika J

A Novel Claudin 16 Mutation Associated with Childhood Hypercalciuria Abolishes Binding to ZO-1 and Results in Lysosomal Mistargeting Dominik Müller,

Matthew A. Saunders, Jeffrey M. Good, Elizabeth C. Lawrence, Robert E

Identification of Novel pro-α2(IX) Collagen Gene Mutations in Two Families with Distinctive Oligo-Epiphyseal Forms of Multiple Epiphyseal Dysplasia Paul.

Identification of novel polymorphisms in the nuclear protein genes and their relationship with human sperm protamine deficiency and severe male infertility

Presentation transcript:

Phosphoserine Aminotransferase Deficiency: A Novel Disorder of the Serine Biosynthesis Pathway Claire E. Hart, Valerie Race, Younes Achouri, Elsa Wiame, Mark Sharrard, Simon E. Olpin, Jennifer Watkinson, James R. Bonham, Jaak Jaeken, Gert Matthijs, Emile Van Schaftingen The American Journal of Human Genetics Volume 80, Issue 5, Pages 931-937 (May 2007) DOI: 10.1086/517888 Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 1 MRI scans from patient 1 showing generalized atrophy and a hypoplastic cerebellar vermis The American Journal of Human Genetics 2007 80, 931-937DOI: (10.1086/517888) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 2 Mutational analysis of patients 1 and 2. A heterozygous 1-bp deletion in exon 2 and a heterozygous A→C transversion in exon 4, leading to the replacement of the Asp at position 100 with an Ala, were found in the PSAT1 gene. Both patients were also heterozygous for a silent polymorphism in exon 4. In the panels corresponding to exon 2, only the wild-type sequence is shown below each chromatogram. The American Journal of Human Genetics 2007 80, 931-937DOI: (10.1086/517888) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 3 Alignment of Homo sapiens (Hsap) and E. coli (Eco1) phosphoserine aminotransferase. Identical residues are indicated in black. The effect of the mutations found in the patients on the amino acid sequence is indicated above the alignment. The asparagine residue (Ser138) that interacts with the side chain of Asp100 in E. coli phosphoserine aminotransferase is highlighted in gray. The American Journal of Human Genetics 2007 80, 931-937DOI: (10.1086/517888) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 4 Model of the position of Asp93 (equivalent of Asp100) and the neighboring residue Ser138 (equivalent of Asn143) in E. coli phosphoserine aminotransferase. The image was drawn with PyMOL software by use of the E. coli phosphoserine aminotransferase coordinates (Protein Data Bank code 1BJN).10 The American Journal of Human Genetics 2007 80, 931-937DOI: (10.1086/517888) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 5 Purification of recombinant human wild-type and Asp100Ala mutant phosphoserine aminotransferase by chromatography on metal-affinity column. Bacterial extracts were loaded onto a 1-ml His-trapFF affinity column (not shown), which was washed with buffer. Phosphoserine aminotransferase was eluted with a linear imidazole gradient. Fractions were collected as indicated. Samples from the indicated fractions were analyzed by SDS-PAGE. The American Journal of Human Genetics 2007 80, 931-937DOI: (10.1086/517888) Copyright © 2007 The American Society of Human Genetics Terms and Conditions