LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-07-15

AUTHORS

Kirsten M. Farncombe, Emily Thain, Carolina Barnett-Tapia, Hamid Sadeghian, Raymond H. Kim

ABSTRACT

BackgroundNoonan syndrome (NS) is a genetic disorder characterized by developmental delays, typical facial gestalt and cardiovascular defects. LZTR1 variants have been recently described in patients with NS and schwannomatosis, but the association, inheritance pattern and management strategy has not been fully elucidated. Here, we review the contribution of LZTR1 in NS and describe a patient with a novel, likely pathogenic variant in LZTR1.Case presentationA female patient was diagnosed with clinical NS at 8 months of age. She presented in adulthood when a brain and spine MRI identified plexiform neurofibromas; however, she did not meet the clinical criteria for Neurofibromatosis type 1. No pathogenic variants were identified through molecular genetic analysis of NF1, SPRED1 and a multigene NS panel. Whole exome sequencing at age 23 identified a novel de novo likely pathogenic heterozygous variant in the LZTR1 gene denoted as c.743G>A (p.Gly248Glu). Serial MRIs have shown stable imaging findings and the patient is being followed clinically by cardiology, neurology and medical genetics.ConclusionsWe identified a novel mutation in the LZTR1 gene, not previously reported in association with NS. This report provides additional evidence to support for the assessment of schwannomatosis in patients with LZTR1-NS and may have overlap with Neurofibromatosis type 1. More... »

PAGES

160

References to SciGraph publications

  • 2019-02-07. Clinical and mutation profile of pediatric patients with RASopathy-associated hypertrophic cardiomyopathy: results from a Chinese cohort in ORPHANET JOURNAL OF RARE DISEASES
  • 2014-11-06. Assessing copy number from exome sequencing and exome array CGH based on CNV spectrum in a large clinical cohort in GENETICS IN MEDICINE
  • 2018-02-22. Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants in GENETICS IN MEDICINE
  • 2018-10-27. Delineation of LZTR1 mutation-positive patients with Noonan syndrome and identification of LZTR1 binding to RAF1–PPP1CB complexes in HUMAN GENETICS
  • 2013-06-20. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing in GENETICS IN MEDICINE
  • 2020-05-01. Chinese patient with neurofibromatosis-Noonan syndrome caused by novel heterozygous NF1 exons 1–58 deletion: a case report in BMC PEDIATRICS
  • 2015-03-05. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology in GENETICS IN MEDICINE
  • 2013-12-22. Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas in NATURE GENETICS
  • 2016-11-17. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics in GENETICS IN MEDICINE
  • 2007-04. Hyperactive Ras in developmental disorders and cancer in NATURE REVIEWS CANCER
  • 2020-06-08. Digenic inheritance of subclinical variants in Noonan Syndrome patients: an alternative pathogenic model? in EUROPEAN JOURNAL OF HUMAN GENETICS
  • 2018-06-30. Noonan syndrome associated with growth hormone deficiency with biallelic LZTR1 variants in GENETICS IN MEDICINE
  • 2014-10-22. Expanding the mutational spectrum of LZTR1 in schwannomatosis in EUROPEAN JOURNAL OF HUMAN GENETICS
  • 2013-08-05. The integrated landscape of driver genomic alterations in glioblastoma in NATURE GENETICS
  • 2021-01-06. A Chinese family with Noonan syndrome caused by a heterozygous variant in LZTR1: a case report and literature review in BMC ENDOCRINE DISORDERS
  • 2005-09-15. Sequence and structural analysis of BTB domain proteins in GENOME BIOLOGY
  • 2016-08-17. Analysis of protein-coding genetic variation in 60,706 humans in NATURE
  • 2019-07-23. LZTR1 facilitates polyubiquitination and degradation of RAS-GTPases in CELL DEATH & DIFFERENTIATION
  • 2021-07-29. Diagnostic difficulties and possibilities of NF1-like syndromes in childhood in BMC PEDIATRICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12920-022-01304-x

    DOI

    http://dx.doi.org/10.1186/s12920-022-01304-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1149508560

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35840934


    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/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Genetics", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adult", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neurilemmoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neurofibromatoses", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neurofibromatosis 1", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Noonan Syndrome", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Skin Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Young Adult", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada", 
              "id": "http://www.grid.ac/institutes/grid.417184.f", 
              "name": [
                "Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Farncombe", 
            "givenName": "Kirsten M.", 
            "id": "sg:person.0634033126.55", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0634033126.55"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada", 
              "id": "http://www.grid.ac/institutes/grid.415224.4", 
              "name": [
                "Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Thain", 
            "givenName": "Emily", 
            "id": "sg:person.015270052371.18", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015270052371.18"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Ellen and Martin Prossermann Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, Toronto, ON, Canada", 
              "id": "http://www.grid.ac/institutes/grid.417184.f", 
              "name": [
                "Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada", 
                "Ellen and Martin Prossermann Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, Toronto, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Barnett-Tapia", 
            "givenName": "Carolina", 
            "id": "sg:person.01233641110.10", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233641110.10"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Ellen and Martin Prossermann Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, Toronto, ON, Canada", 
              "id": "http://www.grid.ac/institutes/grid.417184.f", 
              "name": [
                "Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada", 
                "Ellen and Martin Prossermann Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, Toronto, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Sadeghian", 
            "givenName": "Hamid", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario Institute for Cancer Research, Department of Medicine, University of Toronto, Toronto, ON, Canada", 
              "id": "http://www.grid.ac/institutes/grid.17063.33", 
              "name": [
                "Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Sinai Health System, Toronto, ON, Canada", 
                "Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario Institute for Cancer Research, Department of Medicine, University of Toronto, Toronto, ON, Canada"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kim", 
            "givenName": "Raymond H.", 
            "id": "sg:person.01171144540.35", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01171144540.35"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/gim.2017.249", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101165582", 
              "https://doi.org/10.1038/gim.2017.249"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13023-019-1010-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1111989433", 
              "https://doi.org/10.1186/s13023-019-1010-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41431-020-0658-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1128290686", 
              "https://doi.org/10.1038/s41431-020-0658-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41436-018-0041-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105215497", 
              "https://doi.org/10.1038/s41436-018-0041-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/gb-2005-6-10-r82", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008496140", 
              "https://doi.org/10.1186/gb-2005-6-10-r82"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature19057", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022281897", 
              "https://doi.org/10.1038/nature19057"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12902-020-00666-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1134387956", 
              "https://doi.org/10.1186/s12902-020-00666-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41418-019-0395-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1119761050", 
              "https://doi.org/10.1038/s41418-019-0395-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ejhg.2014.220", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003386901", 
              "https://doi.org/10.1038/ejhg.2014.220"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00439-018-1951-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1107880510", 
              "https://doi.org/10.1007/s00439-018-1951-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/gim.2016.190", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038769083", 
              "https://doi.org/10.1038/gim.2016.190"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/gim.2013.73", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017226766", 
              "https://doi.org/10.1038/gim.2013.73"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12887-021-02791-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1140038066", 
              "https://doi.org/10.1186/s12887-021-02791-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12887-020-02102-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1127314218", 
              "https://doi.org/10.1186/s12887-020-02102-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2855", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013765746", 
              "https://doi.org/10.1038/ng.2855"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2734", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015195247", 
              "https://doi.org/10.1038/ng.2734"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/gim.2015.30", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022229472", 
              "https://doi.org/10.1038/gim.2015.30"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/gim.2014.160", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025733601", 
              "https://doi.org/10.1038/gim.2014.160"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc2109", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040267703", 
              "https://doi.org/10.1038/nrc2109"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2022-07-15", 
        "datePublishedReg": "2022-07-15", 
        "description": "BackgroundNoonan syndrome (NS) is a genetic disorder characterized by developmental delays, typical facial gestalt and cardiovascular defects. LZTR1 variants have been recently described in patients with NS and schwannomatosis, but the association, inheritance pattern and management strategy has not been fully elucidated. Here, we review the contribution of LZTR1 in NS and describe a patient with a novel, likely pathogenic variant in LZTR1.Case presentationA female patient was diagnosed with clinical NS at 8\u00a0months of age. She presented in adulthood when a brain and spine MRI identified plexiform neurofibromas; however, she did not meet the clinical criteria for Neurofibromatosis type 1. No pathogenic variants were identified through molecular genetic analysis of NF1, SPRED1 and a multigene NS panel. Whole exome sequencing at age 23 identified a novel de novo likely pathogenic heterozygous variant in the LZTR1 gene denoted as c.743G>A (p.Gly248Glu). Serial MRIs have shown stable imaging findings and the patient is being followed clinically by cardiology, neurology and medical genetics.ConclusionsWe identified a novel mutation in the LZTR1 gene, not previously reported in association with NS. This report provides additional evidence to support for the assessment of schwannomatosis in patients with LZTR1-NS and may have overlap with Neurofibromatosis type 1.", 
        "genre": "article", 
        "id": "sg:pub.10.1186/s12920-022-01304-x", 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1039191", 
            "issn": [
              "1755-8794"
            ], 
            "name": "BMC Medical Genomics", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "15"
          }
        ], 
        "keywords": [
          "neurofibromatosis type 1", 
          "LZTR1 gene", 
          "pathogenic variants", 
          "type 1", 
          "stable imaging findings", 
          "pathogenic heterozygous variant", 
          "typical facial gestalt", 
          "months of age", 
          "whole-exome sequencing", 
          "female patients", 
          "imaging findings", 
          "clinical criteria", 
          "serial MRI", 
          "plexiform neurofibroma", 
          "spine MRI", 
          "novel de novo", 
          "patients", 
          "heterozygous variants", 
          "clinical implications", 
          "LZTR1 variants", 
          "Noonan syndrome", 
          "developmental delay", 
          "facial gestalt", 
          "schwannomatosis", 
          "exome sequencing", 
          "age 23", 
          "cardiovascular defects", 
          "genetic disorders", 
          "novel mutations", 
          "syndrome", 
          "MRI", 
          "LZTR1", 
          "molecular genetic analysis", 
          "inheritance pattern", 
          "Medical Genetics", 
          "de novo", 
          "association", 
          "additional evidence", 
          "neurofibromas", 
          "variants", 
          "cardiology", 
          "brain", 
          "months", 
          "neurology", 
          "disorders", 
          "age", 
          "adulthood", 
          "NF1", 
          "genes", 
          "ConclusionsWe", 
          "management strategies", 
          "NS", 
          "SPRED1", 
          "genetic analysis", 
          "report", 
          "findings", 
          "mutations", 
          "novo", 
          "evidence", 
          "assessment", 
          "sequencing", 
          "criteria", 
          "defects", 
          "panel", 
          "genetics", 
          "patterns", 
          "strategies", 
          "delay", 
          "overlap", 
          "analysis", 
          "implications", 
          "gestalt", 
          "contribution"
        ], 
        "name": "LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis", 
        "pagination": "160", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1149508560"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1186/s12920-022-01304-x"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "35840934"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1186/s12920-022-01304-x", 
          "https://app.dimensions.ai/details/publication/pub.1149508560"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-10-01T06:50", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221001/entities/gbq_results/article/article_945.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1186/s12920-022-01304-x"
      }
    ]
     

    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.10.1186/s12920-022-01304-x'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12920-022-01304-x'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12920-022-01304-x'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12920-022-01304-x'


     

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

    294 TRIPLES      21 PREDICATES      129 URIs      102 LITERALS      19 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1186/s12920-022-01304-x schema:about N0b8ef27120934e36a1d8baea5a0a5400
    2 N2262be82f4de4f3eb597ff7d9e941fd6
    3 N25078798bdb94406bd8f9b7c281a2d89
    4 N34139b394fae45439ea111b55dce88b0
    5 N3e37ac91d8be45c2a9fe43d2dfb53c0d
    6 N4a7f0355b33847d58914193f9875c544
    7 N6dcdc2536d15451b9abf6ba8b250057b
    8 N80dd813aa1bf4398afbdae65b0bdc4f9
    9 N9a64919340bc492fadd976b3041ee3f7
    10 Na6e772759a6f43e0af5bc9d5d2e44d8f
    11 Naa78cfd409184a818817879116588756
    12 Ncd62a7dfae81421697e171bcad5d0279
    13 anzsrc-for:06
    14 anzsrc-for:0604
    15 schema:author Ne49bafcf3b6044b6853f57949e38cded
    16 schema:citation sg:pub.10.1007/s00439-018-1951-7
    17 sg:pub.10.1038/ejhg.2014.220
    18 sg:pub.10.1038/gim.2013.73
    19 sg:pub.10.1038/gim.2014.160
    20 sg:pub.10.1038/gim.2015.30
    21 sg:pub.10.1038/gim.2016.190
    22 sg:pub.10.1038/gim.2017.249
    23 sg:pub.10.1038/nature19057
    24 sg:pub.10.1038/ng.2734
    25 sg:pub.10.1038/ng.2855
    26 sg:pub.10.1038/nrc2109
    27 sg:pub.10.1038/s41418-019-0395-5
    28 sg:pub.10.1038/s41431-020-0658-0
    29 sg:pub.10.1038/s41436-018-0041-5
    30 sg:pub.10.1186/gb-2005-6-10-r82
    31 sg:pub.10.1186/s12887-020-02102-z
    32 sg:pub.10.1186/s12887-021-02791-0
    33 sg:pub.10.1186/s12902-020-00666-6
    34 sg:pub.10.1186/s13023-019-1010-z
    35 schema:datePublished 2022-07-15
    36 schema:datePublishedReg 2022-07-15
    37 schema:description BackgroundNoonan syndrome (NS) is a genetic disorder characterized by developmental delays, typical facial gestalt and cardiovascular defects. LZTR1 variants have been recently described in patients with NS and schwannomatosis, but the association, inheritance pattern and management strategy has not been fully elucidated. Here, we review the contribution of LZTR1 in NS and describe a patient with a novel, likely pathogenic variant in LZTR1.Case presentationA female patient was diagnosed with clinical NS at 8 months of age. She presented in adulthood when a brain and spine MRI identified plexiform neurofibromas; however, she did not meet the clinical criteria for Neurofibromatosis type 1. No pathogenic variants were identified through molecular genetic analysis of NF1, SPRED1 and a multigene NS panel. Whole exome sequencing at age 23 identified a novel de novo likely pathogenic heterozygous variant in the LZTR1 gene denoted as c.743G>A (p.Gly248Glu). Serial MRIs have shown stable imaging findings and the patient is being followed clinically by cardiology, neurology and medical genetics.ConclusionsWe identified a novel mutation in the LZTR1 gene, not previously reported in association with NS. This report provides additional evidence to support for the assessment of schwannomatosis in patients with LZTR1-NS and may have overlap with Neurofibromatosis type 1.
    38 schema:genre article
    39 schema:isAccessibleForFree true
    40 schema:isPartOf N10d2e87350e9451fbe5a6a5ebb93bb8d
    41 Nfe4f3735b8d240f193d0a1eb5701275f
    42 sg:journal.1039191
    43 schema:keywords ConclusionsWe
    44 LZTR1
    45 LZTR1 gene
    46 LZTR1 variants
    47 MRI
    48 Medical Genetics
    49 NF1
    50 NS
    51 Noonan syndrome
    52 SPRED1
    53 additional evidence
    54 adulthood
    55 age
    56 age 23
    57 analysis
    58 assessment
    59 association
    60 brain
    61 cardiology
    62 cardiovascular defects
    63 clinical criteria
    64 clinical implications
    65 contribution
    66 criteria
    67 de novo
    68 defects
    69 delay
    70 developmental delay
    71 disorders
    72 evidence
    73 exome sequencing
    74 facial gestalt
    75 female patients
    76 findings
    77 genes
    78 genetic analysis
    79 genetic disorders
    80 genetics
    81 gestalt
    82 heterozygous variants
    83 imaging findings
    84 implications
    85 inheritance pattern
    86 management strategies
    87 molecular genetic analysis
    88 months
    89 months of age
    90 mutations
    91 neurofibromas
    92 neurofibromatosis type 1
    93 neurology
    94 novel de novo
    95 novel mutations
    96 novo
    97 overlap
    98 panel
    99 pathogenic heterozygous variant
    100 pathogenic variants
    101 patients
    102 patterns
    103 plexiform neurofibroma
    104 report
    105 schwannomatosis
    106 sequencing
    107 serial MRI
    108 spine MRI
    109 stable imaging findings
    110 strategies
    111 syndrome
    112 type 1
    113 typical facial gestalt
    114 variants
    115 whole-exome sequencing
    116 schema:name LZTR1 molecular genetic overlap with clinical implications for Noonan syndrome and schwannomatosis
    117 schema:pagination 160
    118 schema:productId N3c406bc626ea45e589ce5de7e804fb76
    119 N7f20eaa23b7145c5bc30700fd5fed511
    120 Nc24b40ea6b624e12820439f1dac43e0d
    121 schema:sameAs https://app.dimensions.ai/details/publication/pub.1149508560
    122 https://doi.org/10.1186/s12920-022-01304-x
    123 schema:sdDatePublished 2022-10-01T06:50
    124 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    125 schema:sdPublisher Nc135d374459043e19b206f828dfec685
    126 schema:url https://doi.org/10.1186/s12920-022-01304-x
    127 sgo:license sg:explorer/license/
    128 sgo:sdDataset articles
    129 rdf:type schema:ScholarlyArticle
    130 N093f3dd321554fde87526ea222680a83 rdf:first sg:person.015270052371.18
    131 rdf:rest Nbee58385d78f493baa665a5ab75c50e4
    132 N0b8ef27120934e36a1d8baea5a0a5400 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    133 schema:name Neurilemmoma
    134 rdf:type schema:DefinedTerm
    135 N10d2e87350e9451fbe5a6a5ebb93bb8d schema:volumeNumber 15
    136 rdf:type schema:PublicationVolume
    137 N2262be82f4de4f3eb597ff7d9e941fd6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    138 schema:name Skin Neoplasms
    139 rdf:type schema:DefinedTerm
    140 N25078798bdb94406bd8f9b7c281a2d89 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name Female
    142 rdf:type schema:DefinedTerm
    143 N34139b394fae45439ea111b55dce88b0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    144 schema:name Neurofibromatoses
    145 rdf:type schema:DefinedTerm
    146 N3c406bc626ea45e589ce5de7e804fb76 schema:name pubmed_id
    147 schema:value 35840934
    148 rdf:type schema:PropertyValue
    149 N3e37ac91d8be45c2a9fe43d2dfb53c0d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Mutation
    151 rdf:type schema:DefinedTerm
    152 N4a7f0355b33847d58914193f9875c544 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    153 schema:name Molecular Biology
    154 rdf:type schema:DefinedTerm
    155 N6387c95c9ef24692888d978128f95f9e schema:affiliation grid-institutes:grid.417184.f
    156 schema:familyName Sadeghian
    157 schema:givenName Hamid
    158 rdf:type schema:Person
    159 N690ba3f9a6b04e18a9cd7a59c763da4e rdf:first N6387c95c9ef24692888d978128f95f9e
    160 rdf:rest N7845671b282f4d76a58d1ade36e8700b
    161 N6dcdc2536d15451b9abf6ba8b250057b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name Transcription Factors
    163 rdf:type schema:DefinedTerm
    164 N7845671b282f4d76a58d1ade36e8700b rdf:first sg:person.01171144540.35
    165 rdf:rest rdf:nil
    166 N7f20eaa23b7145c5bc30700fd5fed511 schema:name dimensions_id
    167 schema:value pub.1149508560
    168 rdf:type schema:PropertyValue
    169 N80dd813aa1bf4398afbdae65b0bdc4f9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    170 schema:name Neurofibromatosis 1
    171 rdf:type schema:DefinedTerm
    172 N9a64919340bc492fadd976b3041ee3f7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    173 schema:name Humans
    174 rdf:type schema:DefinedTerm
    175 Na6e772759a6f43e0af5bc9d5d2e44d8f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    176 schema:name Young Adult
    177 rdf:type schema:DefinedTerm
    178 Naa78cfd409184a818817879116588756 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    179 schema:name Adult
    180 rdf:type schema:DefinedTerm
    181 Nbee58385d78f493baa665a5ab75c50e4 rdf:first sg:person.01233641110.10
    182 rdf:rest N690ba3f9a6b04e18a9cd7a59c763da4e
    183 Nc135d374459043e19b206f828dfec685 schema:name Springer Nature - SN SciGraph project
    184 rdf:type schema:Organization
    185 Nc24b40ea6b624e12820439f1dac43e0d schema:name doi
    186 schema:value 10.1186/s12920-022-01304-x
    187 rdf:type schema:PropertyValue
    188 Ncd62a7dfae81421697e171bcad5d0279 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    189 schema:name Noonan Syndrome
    190 rdf:type schema:DefinedTerm
    191 Ne49bafcf3b6044b6853f57949e38cded rdf:first sg:person.0634033126.55
    192 rdf:rest N093f3dd321554fde87526ea222680a83
    193 Nfe4f3735b8d240f193d0a1eb5701275f schema:issueNumber 1
    194 rdf:type schema:PublicationIssue
    195 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    196 schema:name Biological Sciences
    197 rdf:type schema:DefinedTerm
    198 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    199 schema:name Genetics
    200 rdf:type schema:DefinedTerm
    201 sg:journal.1039191 schema:issn 1755-8794
    202 schema:name BMC Medical Genomics
    203 schema:publisher Springer Nature
    204 rdf:type schema:Periodical
    205 sg:person.01171144540.35 schema:affiliation grid-institutes:grid.17063.33
    206 schema:familyName Kim
    207 schema:givenName Raymond H.
    208 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01171144540.35
    209 rdf:type schema:Person
    210 sg:person.01233641110.10 schema:affiliation grid-institutes:grid.417184.f
    211 schema:familyName Barnett-Tapia
    212 schema:givenName Carolina
    213 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233641110.10
    214 rdf:type schema:Person
    215 sg:person.015270052371.18 schema:affiliation grid-institutes:grid.415224.4
    216 schema:familyName Thain
    217 schema:givenName Emily
    218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015270052371.18
    219 rdf:type schema:Person
    220 sg:person.0634033126.55 schema:affiliation grid-institutes:grid.417184.f
    221 schema:familyName Farncombe
    222 schema:givenName Kirsten M.
    223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0634033126.55
    224 rdf:type schema:Person
    225 sg:pub.10.1007/s00439-018-1951-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107880510
    226 https://doi.org/10.1007/s00439-018-1951-7
    227 rdf:type schema:CreativeWork
    228 sg:pub.10.1038/ejhg.2014.220 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003386901
    229 https://doi.org/10.1038/ejhg.2014.220
    230 rdf:type schema:CreativeWork
    231 sg:pub.10.1038/gim.2013.73 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017226766
    232 https://doi.org/10.1038/gim.2013.73
    233 rdf:type schema:CreativeWork
    234 sg:pub.10.1038/gim.2014.160 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025733601
    235 https://doi.org/10.1038/gim.2014.160
    236 rdf:type schema:CreativeWork
    237 sg:pub.10.1038/gim.2015.30 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022229472
    238 https://doi.org/10.1038/gim.2015.30
    239 rdf:type schema:CreativeWork
    240 sg:pub.10.1038/gim.2016.190 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038769083
    241 https://doi.org/10.1038/gim.2016.190
    242 rdf:type schema:CreativeWork
    243 sg:pub.10.1038/gim.2017.249 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101165582
    244 https://doi.org/10.1038/gim.2017.249
    245 rdf:type schema:CreativeWork
    246 sg:pub.10.1038/nature19057 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022281897
    247 https://doi.org/10.1038/nature19057
    248 rdf:type schema:CreativeWork
    249 sg:pub.10.1038/ng.2734 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015195247
    250 https://doi.org/10.1038/ng.2734
    251 rdf:type schema:CreativeWork
    252 sg:pub.10.1038/ng.2855 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013765746
    253 https://doi.org/10.1038/ng.2855
    254 rdf:type schema:CreativeWork
    255 sg:pub.10.1038/nrc2109 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040267703
    256 https://doi.org/10.1038/nrc2109
    257 rdf:type schema:CreativeWork
    258 sg:pub.10.1038/s41418-019-0395-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1119761050
    259 https://doi.org/10.1038/s41418-019-0395-5
    260 rdf:type schema:CreativeWork
    261 sg:pub.10.1038/s41431-020-0658-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1128290686
    262 https://doi.org/10.1038/s41431-020-0658-0
    263 rdf:type schema:CreativeWork
    264 sg:pub.10.1038/s41436-018-0041-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105215497
    265 https://doi.org/10.1038/s41436-018-0041-5
    266 rdf:type schema:CreativeWork
    267 sg:pub.10.1186/gb-2005-6-10-r82 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008496140
    268 https://doi.org/10.1186/gb-2005-6-10-r82
    269 rdf:type schema:CreativeWork
    270 sg:pub.10.1186/s12887-020-02102-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1127314218
    271 https://doi.org/10.1186/s12887-020-02102-z
    272 rdf:type schema:CreativeWork
    273 sg:pub.10.1186/s12887-021-02791-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1140038066
    274 https://doi.org/10.1186/s12887-021-02791-0
    275 rdf:type schema:CreativeWork
    276 sg:pub.10.1186/s12902-020-00666-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1134387956
    277 https://doi.org/10.1186/s12902-020-00666-6
    278 rdf:type schema:CreativeWork
    279 sg:pub.10.1186/s13023-019-1010-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1111989433
    280 https://doi.org/10.1186/s13023-019-1010-z
    281 rdf:type schema:CreativeWork
    282 grid-institutes:grid.17063.33 schema:alternateName Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario Institute for Cancer Research, Department of Medicine, University of Toronto, Toronto, ON, Canada
    283 schema:name Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario Institute for Cancer Research, Department of Medicine, University of Toronto, Toronto, ON, Canada
    284 Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Sinai Health System, Toronto, ON, Canada
    285 rdf:type schema:Organization
    286 grid-institutes:grid.415224.4 schema:alternateName Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
    287 schema:name Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
    288 rdf:type schema:Organization
    289 grid-institutes:grid.417184.f schema:alternateName Ellen and Martin Prossermann Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, Toronto, ON, Canada
    290 Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
    291 schema:name Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada
    292 Ellen and Martin Prossermann Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, Toronto, ON, Canada
    293 Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
    294 rdf:type schema:Organization
     




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


    ...