A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-01-24

AUTHORS

Simon Julius Mayr, Jörn Oliver Sass, Julia Vry, Janbernd Kirschner, Irina Mader, Jan-Bernd Hövener, Jochen Reiss, José Angel Santamaria-Araujo, Günter Schwarz, Sarah Catharina Grünert

ABSTRACT

Molybdenum cofactor deficiency is an autosomal recessive inborn error of metabolism, which results from mutations in genes involved in Moco biosynthesis. Moco serves as a cofactor of several enzymes, including sulfite oxidase. MoCD is clinically characterized by intractable seizures and severe, rapidly progressing neurodegeneration leading to death in early childhood in the majority of known cases. Here we report a patient with an unusual late disease onset and mild phenotype, characterized by a lack of seizures, normal early development, a decline triggered by febrile illness and a subsequent dystonic movement disorder. Genetic analysis revealed a homozygous c.1338delG MOCS1 mutation causing a frameshift (p.S442fs) with a premature termination of the MOCS1AB translation product at position 477 lacking the entire MOCS1B domain. Surprisingly, urine analysis detected trace amounts (1% of control) of the Moco degradation product urothione, suggesting a residual Moco synthesis in the patient, which was consistent with the mild clinical presentation. Therefore, we performed bioinformatic analysis of the patient’s mutated MOCS1 transcript and found a potential Kozak-sequence downstream of the mutation site providing the possibility of an independent expression of a MOCS1B protein. Following the expression of the patient’s MOCS1 cDNA in HEK293 cells we detected two proteins: a truncated MOCS1AB protein and a 22.4 kDa protein representing MOCS1B. Functional studies of both proteins confirmed activity of MOCS1B, but not of the truncated MOCS1AB. This finding demonstrates an unusual mechanism of translation re-initiation in the MOCS1 transcript, which results in trace amounts of functional MOCS1B protein being sufficient to partially protect the patient from the most severe symptoms of MoCD. More... »

PAGES

187-196

Journal

TITLE

Journal of Inherited Metabolic Disease

ISSUE

2

VOLUME

41

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10545-018-0138-7

DOI

http://dx.doi.org/10.1007/s10545-018-0138-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100618409

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29368224


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Clinical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Age of Onset", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carbon-Carbon Lyases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Child", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Child, Preschool", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Coenzymes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Diet, Protein-Restricted", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Frameshift Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genetic Predisposition to Disease", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "HEK293 Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Magnetic Resonance Imaging", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Metal Metabolism, Inborn Errors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Metalloproteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Molybdenum Cofactors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Nuclear Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Peptide Fragments", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Phenotype", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Pteridines", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Institute of Biochemistry, Department of Chemistry, University of Cologne, Z\u00fclpicher Str. 47, 50674, K\u00f6ln, Germany", 
          "id": "http://www.grid.ac/institutes/grid.6190.e", 
          "name": [
            "Institute of Biochemistry, Department of Chemistry, University of Cologne, Z\u00fclpicher Str. 47, 50674, K\u00f6ln, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mayr", 
        "givenName": "Simon Julius", 
        "id": "sg:person.07447665374.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07447665374.35"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Bioanalytics & Biochemistry, Department of Natural Science, Bonn-Rhein Sieg University of Applied Sciences, Rheinbach, Germany", 
          "id": "http://www.grid.ac/institutes/grid.425058.e", 
          "name": [
            "Bioanalytics & Biochemistry, Department of Natural Science, Bonn-Rhein Sieg University of Applied Sciences, Rheinbach, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sass", 
        "givenName": "J\u00f6rn Oliver", 
        "id": "sg:person.0734611746.36", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0734611746.36"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center \u2013 University of Freiburg, Freiburg, Germany", 
          "id": "http://www.grid.ac/institutes/grid.7708.8", 
          "name": [
            "Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center \u2013 University of Freiburg, Freiburg, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Vry", 
        "givenName": "Julia", 
        "id": "sg:person.01013442311.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01013442311.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center \u2013 University of Freiburg, Freiburg, Germany", 
          "id": "http://www.grid.ac/institutes/grid.7708.8", 
          "name": [
            "Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center \u2013 University of Freiburg, Freiburg, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kirschner", 
        "givenName": "Janbernd", 
        "id": "sg:person.0717435623.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717435623.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Faculty of Medicine, Department of Neuroradiology, University of Freiburg, Freiburg, Germany", 
          "id": "http://www.grid.ac/institutes/grid.5963.9", 
          "name": [
            "Faculty of Medicine, Department of Neuroradiology, University of Freiburg, Freiburg, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mader", 
        "givenName": "Irina", 
        "id": "sg:person.01102224222.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01102224222.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Section for Biomedical Imaging and MOIN CC, University Medical Center Schleswig Holstein, University of Kiel, Kiel, Germany", 
          "id": "http://www.grid.ac/institutes/grid.9764.c", 
          "name": [
            "Department of Radiology, Medical Physics, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany", 
            "Section for Biomedical Imaging and MOIN CC, University Medical Center Schleswig Holstein, University of Kiel, Kiel, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "H\u00f6vener", 
        "givenName": "Jan-Bernd", 
        "id": "sg:person.01300576661.98", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300576661.98"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institut f\u00fcr Humangenetik, Universit\u00e4t G\u00f6ttingen, G\u00f6ttingen, Germany", 
          "id": "http://www.grid.ac/institutes/grid.7450.6", 
          "name": [
            "Institut f\u00fcr Humangenetik, Universit\u00e4t G\u00f6ttingen, G\u00f6ttingen, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Reiss", 
        "givenName": "Jochen", 
        "id": "sg:person.01266221510.17", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01266221510.17"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Biochemistry, Department of Chemistry, University of Cologne, Z\u00fclpicher Str. 47, 50674, K\u00f6ln, Germany", 
          "id": "http://www.grid.ac/institutes/grid.6190.e", 
          "name": [
            "Institute of Biochemistry, Department of Chemistry, University of Cologne, Z\u00fclpicher Str. 47, 50674, K\u00f6ln, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Santamaria-Araujo", 
        "givenName": "Jos\u00e9 Angel", 
        "id": "sg:person.0717424024.19", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717424024.19"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Center for Molecular Medicine Cologne), University of Cologne, Cologne, Germany", 
          "id": "http://www.grid.ac/institutes/grid.6190.e", 
          "name": [
            "Institute of Biochemistry, Department of Chemistry, University of Cologne, Z\u00fclpicher Str. 47, 50674, K\u00f6ln, Germany", 
            "Center for Molecular Medicine Cologne), University of Cologne, Cologne, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Schwarz", 
        "givenName": "G\u00fcnter", 
        "id": "sg:person.010531725702.83", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010531725702.83"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center \u2013 University of Freiburg, Mathildenstr. 1, 79106, Freiburg, Germany", 
          "id": "http://www.grid.ac/institutes/grid.7708.8", 
          "name": [
            "Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center \u2013 University of Freiburg, Mathildenstr. 1, 79106, Freiburg, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gr\u00fcnert", 
        "givenName": "Sarah Catharina", 
        "id": "sg:person.01054073227.68", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054073227.68"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1186/s13023-016-0436-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027629700", 
          "https://doi.org/10.1186/s13023-016-0436-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/978-94-007-7500-8_13", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037303946", 
          "https://doi.org/10.1007/978-94-007-7500-8_13"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/gim.2015.12", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053566774", 
          "https://doi.org/10.1038/gim.2015.12"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1479-7364-4-2-119", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1078028983", 
          "https://doi.org/10.1186/1479-7364-4-2-119"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10545-009-1151-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050895613", 
          "https://doi.org/10.1007/s10545-009-1151-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/978-1-4615-2960-6_77", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016152743", 
          "https://doi.org/10.1007/978-1-4615-2960-6_77"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/8904_2011_89", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002413304", 
          "https://doi.org/10.1007/8904_2011_89"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-01-24", 
    "datePublishedReg": "2018-01-24", 
    "description": "Molybdenum cofactor deficiency is an autosomal recessive inborn error of metabolism, which results from mutations in genes involved in Moco biosynthesis. Moco serves as a cofactor of several enzymes, including sulfite oxidase. MoCD is clinically characterized by intractable seizures and severe, rapidly progressing neurodegeneration leading to death in early childhood in the majority of known cases. Here we report a patient with an unusual late disease onset and mild phenotype, characterized by a lack of seizures, normal early development, a decline triggered by febrile illness and a subsequent dystonic movement disorder. Genetic analysis revealed a homozygous c.1338delG MOCS1 mutation causing a frameshift (p.S442fs) with a premature termination of the MOCS1AB translation product at position 477 lacking the entire MOCS1B domain. Surprisingly, urine analysis detected trace amounts (1% of control) of the Moco degradation product urothione, suggesting a residual Moco synthesis in the patient, which was consistent with the mild clinical presentation. Therefore, we performed bioinformatic analysis of the patient\u2019s mutated MOCS1 transcript and found a potential Kozak-sequence downstream of the mutation site providing the possibility of an independent expression of a MOCS1B protein. Following the expression of the patient\u2019s MOCS1 cDNA in HEK293 cells we detected two proteins: a truncated MOCS1AB protein and a 22.4 kDa protein representing MOCS1B. Functional studies of both proteins confirmed activity of MOCS1B, but not of the truncated MOCS1AB. This finding demonstrates an unusual mechanism of translation re-initiation in the MOCS1 transcript, which results in trace amounts of functional MOCS1B protein being sufficient to partially protect the patient from the most severe symptoms of MoCD.", 
    "genre": "article", 
    "id": "sg:pub.10.1007/s10545-018-0138-7", 
    "inLanguage": "en", 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1090550", 
        "issn": [
          "0141-8955", 
          "1573-2665"
        ], 
        "name": "Journal of Inherited Metabolic Disease", 
        "publisher": "Wiley", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "2", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "41"
      }
    ], 
    "keywords": [
      "Moco biosynthesis", 
      "protein maturation", 
      "bioinformatics analysis", 
      "translation products", 
      "Moco synthesis", 
      "genetic analysis", 
      "position 477", 
      "HEK293 cells", 
      "functional studies", 
      "molybdenum cofactor deficiency", 
      "mutation sites", 
      "MOCS1 mutation", 
      "protein", 
      "independent expression", 
      "unusual mechanism", 
      "premature termination", 
      "early development", 
      "mild phenotype", 
      "transcripts", 
      "mutations", 
      "sulfite oxidase", 
      "normal early development", 
      "cofactor deficiency", 
      "MOCS1B", 
      "expression", 
      "biosynthesis", 
      "cDNA", 
      "genes", 
      "Moco", 
      "autosomal recessive inborn error", 
      "cofactor", 
      "frameshift", 
      "recessive inborn error", 
      "phenotype", 
      "enzyme", 
      "inborn errors", 
      "MoCD", 
      "trace amounts", 
      "maturation", 
      "metabolism", 
      "neurodegeneration", 
      "downstream", 
      "oxidase", 
      "cells", 
      "deficiency", 
      "domain", 
      "translation", 
      "sites", 
      "mechanism", 
      "analysis", 
      "activity", 
      "alternative route", 
      "decline", 
      "death", 
      "lack of seizures", 
      "amount", 
      "synthesis", 
      "development", 
      "dystonic movement disorder", 
      "disease onset", 
      "majority", 
      "termination", 
      "products", 
      "late disease onset", 
      "urothione", 
      "findings", 
      "lack", 
      "severe symptoms", 
      "mild clinical presentation", 
      "study", 
      "disorders", 
      "possibility", 
      "movement disorders", 
      "onset", 
      "route", 
      "intractable seizures", 
      "cases", 
      "febrile illness", 
      "seizures", 
      "patients", 
      "symptoms", 
      "clinical presentation", 
      "early childhood", 
      "presentation", 
      "mild cases", 
      "illness", 
      "childhood", 
      "error", 
      "urine analysis"
    ], 
    "name": "A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation", 
    "pagination": "187-196", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1100618409"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s10545-018-0138-7"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29368224"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s10545-018-0138-7", 
      "https://app.dimensions.ai/details/publication/pub.1100618409"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-05-10T10:21", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220509/entities/gbq_results/article/article_776.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1007/s10545-018-0138-7"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s10545-018-0138-7'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10545-018-0138-7'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10545-018-0138-7'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10545-018-0138-7'


 

This table displays all metadata directly associated to this object as RDF triples.

338 TRIPLES      22 PREDICATES      141 URIs      126 LITERALS      26 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s10545-018-0138-7 schema:about N0dc6a0f270ce4bd09da4edecbdbaff6c
2 N103993b84ed44a4fb7c46e137c8f4d35
3 N116846c3d62b449ab176aab64f241faa
4 N193a01db287542209dd3412d183b5f21
5 N3f3f7050eb214597a01e75b94a92b918
6 N42a20923425a44f0944a11adc6e93186
7 N4e16a1e459dd486ab95b63f3466c6309
8 N659668f452e1426abca9fbcf544cef69
9 N83b39ef5743644d181bccf4c05f86712
10 N972403b1274a42c28fe356406f8334b5
11 N9758a141a06244cc82835ce245b7d126
12 N9845305e2dd440988ae66929bde1389d
13 N9a87058408fb4963b80aa4e03b17d130
14 Na3a34ec9c78f43b0bf2c55d2b09e3351
15 Naad1a0724082447084f7ecfd85c1f0ac
16 Nc9e7ca8ded2d4696bbb61a082400eebd
17 Ncc7ec0c129c7410d8ea8d7ffaf937f40
18 Ned97c33405e14601b36095f2f1a814c5
19 Nf8c8db8c7a8a441397804488a31a87e2
20 anzsrc-for:11
21 anzsrc-for:1103
22 schema:author N897c7d507ef54e64884412214c328fb9
23 schema:citation sg:pub.10.1007/8904_2011_89
24 sg:pub.10.1007/978-1-4615-2960-6_77
25 sg:pub.10.1007/978-94-007-7500-8_13
26 sg:pub.10.1007/s10545-009-1151-7
27 sg:pub.10.1038/gim.2015.12
28 sg:pub.10.1186/1479-7364-4-2-119
29 sg:pub.10.1186/s13023-016-0436-9
30 schema:datePublished 2018-01-24
31 schema:datePublishedReg 2018-01-24
32 schema:description Molybdenum cofactor deficiency is an autosomal recessive inborn error of metabolism, which results from mutations in genes involved in Moco biosynthesis. Moco serves as a cofactor of several enzymes, including sulfite oxidase. MoCD is clinically characterized by intractable seizures and severe, rapidly progressing neurodegeneration leading to death in early childhood in the majority of known cases. Here we report a patient with an unusual late disease onset and mild phenotype, characterized by a lack of seizures, normal early development, a decline triggered by febrile illness and a subsequent dystonic movement disorder. Genetic analysis revealed a homozygous c.1338delG MOCS1 mutation causing a frameshift (p.S442fs) with a premature termination of the MOCS1AB translation product at position 477 lacking the entire MOCS1B domain. Surprisingly, urine analysis detected trace amounts (1% of control) of the Moco degradation product urothione, suggesting a residual Moco synthesis in the patient, which was consistent with the mild clinical presentation. Therefore, we performed bioinformatic analysis of the patient’s mutated MOCS1 transcript and found a potential Kozak-sequence downstream of the mutation site providing the possibility of an independent expression of a MOCS1B protein. Following the expression of the patient’s MOCS1 cDNA in HEK293 cells we detected two proteins: a truncated MOCS1AB protein and a 22.4 kDa protein representing MOCS1B. Functional studies of both proteins confirmed activity of MOCS1B, but not of the truncated MOCS1AB. This finding demonstrates an unusual mechanism of translation re-initiation in the MOCS1 transcript, which results in trace amounts of functional MOCS1B protein being sufficient to partially protect the patient from the most severe symptoms of MoCD.
33 schema:genre article
34 schema:inLanguage en
35 schema:isAccessibleForFree false
36 schema:isPartOf N414f017ec43a40df8a02eea09c2e18ab
37 Nc31be9a2ee664c968b83ce6a45c61029
38 sg:journal.1090550
39 schema:keywords HEK293 cells
40 MOCS1 mutation
41 MOCS1B
42 MoCD
43 Moco
44 Moco biosynthesis
45 Moco synthesis
46 activity
47 alternative route
48 amount
49 analysis
50 autosomal recessive inborn error
51 bioinformatics analysis
52 biosynthesis
53 cDNA
54 cases
55 cells
56 childhood
57 clinical presentation
58 cofactor
59 cofactor deficiency
60 death
61 decline
62 deficiency
63 development
64 disease onset
65 disorders
66 domain
67 downstream
68 dystonic movement disorder
69 early childhood
70 early development
71 enzyme
72 error
73 expression
74 febrile illness
75 findings
76 frameshift
77 functional studies
78 genes
79 genetic analysis
80 illness
81 inborn errors
82 independent expression
83 intractable seizures
84 lack
85 lack of seizures
86 late disease onset
87 majority
88 maturation
89 mechanism
90 metabolism
91 mild cases
92 mild clinical presentation
93 mild phenotype
94 molybdenum cofactor deficiency
95 movement disorders
96 mutation sites
97 mutations
98 neurodegeneration
99 normal early development
100 onset
101 oxidase
102 patients
103 phenotype
104 position 477
105 possibility
106 premature termination
107 presentation
108 products
109 protein
110 protein maturation
111 recessive inborn error
112 route
113 seizures
114 severe symptoms
115 sites
116 study
117 sulfite oxidase
118 symptoms
119 synthesis
120 termination
121 trace amounts
122 transcripts
123 translation
124 translation products
125 unusual mechanism
126 urine analysis
127 urothione
128 schema:name A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation
129 schema:pagination 187-196
130 schema:productId N3f273e4223be46eb83027a7432e07dbe
131 N4cb3d6d40894446981bc8fe8a5e804dd
132 N4ff0863d157a491895ab43a24b9f9440
133 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100618409
134 https://doi.org/10.1007/s10545-018-0138-7
135 schema:sdDatePublished 2022-05-10T10:21
136 schema:sdLicense https://scigraph.springernature.com/explorer/license/
137 schema:sdPublisher N7eaa286de0214cb8928c76f52c92cc14
138 schema:url https://doi.org/10.1007/s10545-018-0138-7
139 sgo:license sg:explorer/license/
140 sgo:sdDataset articles
141 rdf:type schema:ScholarlyArticle
142 N091377bdf4c84b498caf680e378276a0 rdf:first sg:person.01266221510.17
143 rdf:rest N745076e7dce441b38f6eff5a017767d0
144 N0dc6a0f270ce4bd09da4edecbdbaff6c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
145 schema:name Carbon-Carbon Lyases
146 rdf:type schema:DefinedTerm
147 N103993b84ed44a4fb7c46e137c8f4d35 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Metalloproteins
149 rdf:type schema:DefinedTerm
150 N116846c3d62b449ab176aab64f241faa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
151 schema:name Magnetic Resonance Imaging
152 rdf:type schema:DefinedTerm
153 N193a01db287542209dd3412d183b5f21 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
154 schema:name Peptide Fragments
155 rdf:type schema:DefinedTerm
156 N3f273e4223be46eb83027a7432e07dbe schema:name pubmed_id
157 schema:value 29368224
158 rdf:type schema:PropertyValue
159 N3f3f7050eb214597a01e75b94a92b918 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
160 schema:name Pteridines
161 rdf:type schema:DefinedTerm
162 N414f017ec43a40df8a02eea09c2e18ab schema:volumeNumber 41
163 rdf:type schema:PublicationVolume
164 N42a20923425a44f0944a11adc6e93186 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
165 schema:name Male
166 rdf:type schema:DefinedTerm
167 N4cb3d6d40894446981bc8fe8a5e804dd schema:name doi
168 schema:value 10.1007/s10545-018-0138-7
169 rdf:type schema:PropertyValue
170 N4e16a1e459dd486ab95b63f3466c6309 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
171 schema:name Child, Preschool
172 rdf:type schema:DefinedTerm
173 N4ff0863d157a491895ab43a24b9f9440 schema:name dimensions_id
174 schema:value pub.1100618409
175 rdf:type schema:PropertyValue
176 N659668f452e1426abca9fbcf544cef69 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Child
178 rdf:type schema:DefinedTerm
179 N745076e7dce441b38f6eff5a017767d0 rdf:first sg:person.0717424024.19
180 rdf:rest N8e1f01b64f2f47d991d220582b2d0ea5
181 N7eaa286de0214cb8928c76f52c92cc14 schema:name Springer Nature - SN SciGraph project
182 rdf:type schema:Organization
183 N83b39ef5743644d181bccf4c05f86712 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
184 schema:name Nuclear Proteins
185 rdf:type schema:DefinedTerm
186 N897c7d507ef54e64884412214c328fb9 rdf:first sg:person.07447665374.35
187 rdf:rest Nfd1a18deec1a45ee996f81923b9f0929
188 N8e1f01b64f2f47d991d220582b2d0ea5 rdf:first sg:person.010531725702.83
189 rdf:rest Nef3dafd14f8c42f8b620b776b705e666
190 N972403b1274a42c28fe356406f8334b5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
191 schema:name Age of Onset
192 rdf:type schema:DefinedTerm
193 N9758a141a06244cc82835ce245b7d126 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
194 schema:name Humans
195 rdf:type schema:DefinedTerm
196 N97695cef178e4e9fa070e89661aa7214 rdf:first sg:person.01300576661.98
197 rdf:rest N091377bdf4c84b498caf680e378276a0
198 N9845305e2dd440988ae66929bde1389d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
199 schema:name HEK293 Cells
200 rdf:type schema:DefinedTerm
201 N99bd81ed7cd341e29b5e1dfa383132e3 rdf:first sg:person.01102224222.44
202 rdf:rest N97695cef178e4e9fa070e89661aa7214
203 N9a87058408fb4963b80aa4e03b17d130 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
204 schema:name Coenzymes
205 rdf:type schema:DefinedTerm
206 Na3a34ec9c78f43b0bf2c55d2b09e3351 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
207 schema:name Genetic Predisposition to Disease
208 rdf:type schema:DefinedTerm
209 Na406a72d6aa94caaa3ff99ce0921c5ce rdf:first sg:person.0717435623.02
210 rdf:rest N99bd81ed7cd341e29b5e1dfa383132e3
211 Naad1a0724082447084f7ecfd85c1f0ac schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
212 schema:name Diet, Protein-Restricted
213 rdf:type schema:DefinedTerm
214 Nc31be9a2ee664c968b83ce6a45c61029 schema:issueNumber 2
215 rdf:type schema:PublicationIssue
216 Nc9e7ca8ded2d4696bbb61a082400eebd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
217 schema:name Molybdenum Cofactors
218 rdf:type schema:DefinedTerm
219 Ncc7ec0c129c7410d8ea8d7ffaf937f40 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
220 schema:name Phenotype
221 rdf:type schema:DefinedTerm
222 Ned97c33405e14601b36095f2f1a814c5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
223 schema:name Frameshift Mutation
224 rdf:type schema:DefinedTerm
225 Nee0a0f2c7bb34f39aef152e2e8173858 rdf:first sg:person.01013442311.43
226 rdf:rest Na406a72d6aa94caaa3ff99ce0921c5ce
227 Nef3dafd14f8c42f8b620b776b705e666 rdf:first sg:person.01054073227.68
228 rdf:rest rdf:nil
229 Nf8c8db8c7a8a441397804488a31a87e2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
230 schema:name Metal Metabolism, Inborn Errors
231 rdf:type schema:DefinedTerm
232 Nfd1a18deec1a45ee996f81923b9f0929 rdf:first sg:person.0734611746.36
233 rdf:rest Nee0a0f2c7bb34f39aef152e2e8173858
234 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
235 schema:name Medical and Health Sciences
236 rdf:type schema:DefinedTerm
237 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
238 schema:name Clinical Sciences
239 rdf:type schema:DefinedTerm
240 sg:journal.1090550 schema:issn 0141-8955
241 1573-2665
242 schema:name Journal of Inherited Metabolic Disease
243 schema:publisher Wiley
244 rdf:type schema:Periodical
245 sg:person.01013442311.43 schema:affiliation grid-institutes:grid.7708.8
246 schema:familyName Vry
247 schema:givenName Julia
248 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01013442311.43
249 rdf:type schema:Person
250 sg:person.010531725702.83 schema:affiliation grid-institutes:grid.6190.e
251 schema:familyName Schwarz
252 schema:givenName Günter
253 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010531725702.83
254 rdf:type schema:Person
255 sg:person.01054073227.68 schema:affiliation grid-institutes:grid.7708.8
256 schema:familyName Grünert
257 schema:givenName Sarah Catharina
258 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054073227.68
259 rdf:type schema:Person
260 sg:person.01102224222.44 schema:affiliation grid-institutes:grid.5963.9
261 schema:familyName Mader
262 schema:givenName Irina
263 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01102224222.44
264 rdf:type schema:Person
265 sg:person.01266221510.17 schema:affiliation grid-institutes:grid.7450.6
266 schema:familyName Reiss
267 schema:givenName Jochen
268 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01266221510.17
269 rdf:type schema:Person
270 sg:person.01300576661.98 schema:affiliation grid-institutes:grid.9764.c
271 schema:familyName Hövener
272 schema:givenName Jan-Bernd
273 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01300576661.98
274 rdf:type schema:Person
275 sg:person.0717424024.19 schema:affiliation grid-institutes:grid.6190.e
276 schema:familyName Santamaria-Araujo
277 schema:givenName José Angel
278 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717424024.19
279 rdf:type schema:Person
280 sg:person.0717435623.02 schema:affiliation grid-institutes:grid.7708.8
281 schema:familyName Kirschner
282 schema:givenName Janbernd
283 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717435623.02
284 rdf:type schema:Person
285 sg:person.0734611746.36 schema:affiliation grid-institutes:grid.425058.e
286 schema:familyName Sass
287 schema:givenName Jörn Oliver
288 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0734611746.36
289 rdf:type schema:Person
290 sg:person.07447665374.35 schema:affiliation grid-institutes:grid.6190.e
291 schema:familyName Mayr
292 schema:givenName Simon Julius
293 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07447665374.35
294 rdf:type schema:Person
295 sg:pub.10.1007/8904_2011_89 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002413304
296 https://doi.org/10.1007/8904_2011_89
297 rdf:type schema:CreativeWork
298 sg:pub.10.1007/978-1-4615-2960-6_77 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016152743
299 https://doi.org/10.1007/978-1-4615-2960-6_77
300 rdf:type schema:CreativeWork
301 sg:pub.10.1007/978-94-007-7500-8_13 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037303946
302 https://doi.org/10.1007/978-94-007-7500-8_13
303 rdf:type schema:CreativeWork
304 sg:pub.10.1007/s10545-009-1151-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050895613
305 https://doi.org/10.1007/s10545-009-1151-7
306 rdf:type schema:CreativeWork
307 sg:pub.10.1038/gim.2015.12 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053566774
308 https://doi.org/10.1038/gim.2015.12
309 rdf:type schema:CreativeWork
310 sg:pub.10.1186/1479-7364-4-2-119 schema:sameAs https://app.dimensions.ai/details/publication/pub.1078028983
311 https://doi.org/10.1186/1479-7364-4-2-119
312 rdf:type schema:CreativeWork
313 sg:pub.10.1186/s13023-016-0436-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027629700
314 https://doi.org/10.1186/s13023-016-0436-9
315 rdf:type schema:CreativeWork
316 grid-institutes:grid.425058.e schema:alternateName Bioanalytics & Biochemistry, Department of Natural Science, Bonn-Rhein Sieg University of Applied Sciences, Rheinbach, Germany
317 schema:name Bioanalytics & Biochemistry, Department of Natural Science, Bonn-Rhein Sieg University of Applied Sciences, Rheinbach, Germany
318 rdf:type schema:Organization
319 grid-institutes:grid.5963.9 schema:alternateName Faculty of Medicine, Department of Neuroradiology, University of Freiburg, Freiburg, Germany
320 schema:name Faculty of Medicine, Department of Neuroradiology, University of Freiburg, Freiburg, Germany
321 rdf:type schema:Organization
322 grid-institutes:grid.6190.e schema:alternateName Center for Molecular Medicine Cologne), University of Cologne, Cologne, Germany
323 Institute of Biochemistry, Department of Chemistry, University of Cologne, Zülpicher Str. 47, 50674, Köln, Germany
324 schema:name Center for Molecular Medicine Cologne), University of Cologne, Cologne, Germany
325 Institute of Biochemistry, Department of Chemistry, University of Cologne, Zülpicher Str. 47, 50674, Köln, Germany
326 rdf:type schema:Organization
327 grid-institutes:grid.7450.6 schema:alternateName Institut für Humangenetik, Universität Göttingen, Göttingen, Germany
328 schema:name Institut für Humangenetik, Universität Göttingen, Göttingen, Germany
329 rdf:type schema:Organization
330 grid-institutes:grid.7708.8 schema:alternateName Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center – University of Freiburg, Mathildenstr. 1, 79106, Freiburg, Germany
331 Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, Germany
332 schema:name Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center – University of Freiburg, Mathildenstr. 1, 79106, Freiburg, Germany
333 Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center – University of Freiburg, Freiburg, Germany
334 rdf:type schema:Organization
335 grid-institutes:grid.9764.c schema:alternateName Section for Biomedical Imaging and MOIN CC, University Medical Center Schleswig Holstein, University of Kiel, Kiel, Germany
336 schema:name Department of Radiology, Medical Physics, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
337 Section for Biomedical Imaging and MOIN CC, University Medical Center Schleswig Holstein, University of Kiel, Kiel, Germany
338 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...