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Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders

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  • معلومة اضافية
    • Contributors:
      CHU Marseille; Marseille medical genetics - Centre de génétique médicale de Marseille (MMG); Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM); Hôpital Archet 2 Nice (CHU); Hospices Civils de Lyon (HCL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon; AP-HP Hôpital universitaire Robert-Debré Paris; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Equipe BIOETHICS (CERPOP); Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP); Université Toulouse III - Paul Sabatier (UT3); Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3); Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); Université de Reims Champagne-Ardenne (URCA); Centre Hospitalier Métropole Savoie Chambéry
    • بيانات النشر:
      HAL CCSD
      BioMed Central
    • الموضوع:
      2019
    • Collection:
      Aix-Marseille Université: HAL
    • نبذة مختصرة :
      International audience ; Background: Segmental progeroid syndromes are a heterogeneous group of rare and often severe genetic disorders that have been studied since the twentieth century. These progeroid syndromes are defined as segmental because only some of the features observed during natural aging are accelerated.Methods: Since 2015, the Molecular Genetics Laboratory in Marseille La Timone Hospital proposes molecular diagnosis of premature aging syndromes including laminopathies and related disorders upon NGS sequencing of a panel of 82 genes involved in these syndromes. We analyzed the results obtained in 4 years on 66 patients issued from France and abroad.Results: Globally, pathogenic or likely pathogenic variants (ACMG class 5 or 4) were identified in about 1/4 of the cases; among these, 9 pathogenic variants were novel. On the other hand, the diagnostic yield of our panel was over 60% when the patients were addressed upon a nosologically specific clinical suspicion, excepted for connective tissue disorders, for which clinical diagnosis may be more challenging. Prenatal testing was proposed to 3 families. We additionally detected 16 variants of uncertain significance and reclassified 3 of them as benign upon segregation analysis in first degree relatives.Conclusions: High throughput sequencing using the Laminopathies/ Premature Aging disorders panel allowed molecular diagnosis of rare disorders associated with premature aging features and genetic counseling for families, representing an interesting first-level analysis before whole genome sequencing may be proposed, as a future second step, by the National high throughput sequencing platforms (“Medicine France Genomics 2025” Plan), in families without molecular diagnosis.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/31829210; hal-04675356; https://hal.science/hal-04675356; https://hal.science/hal-04675356/document; https://hal.science/hal-04675356/file/GRELET_2019.pdf; PUBMED: 31829210; PUBMEDCENTRAL: PMC6907233
    • الرقم المعرف:
      10.1186/s13023-019-1189-z
    • الدخول الالكتروني :
      https://hal.science/hal-04675356
      https://hal.science/hal-04675356/document
      https://hal.science/hal-04675356/file/GRELET_2019.pdf
      https://doi.org/10.1186/s13023-019-1189-z
    • Rights:
      http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.3CB47CDB