Molecular diagnostic workflow, clinical interpretation of sequence variants, and data repository procedures in 140 individuals with familial cerebral cavernous malformations

Research output: Contribution to journalArticle

Abstract

Familial cerebral cavernous malformation (FCCM) is an autosomal dominant vascular disorder caused by heterozygous deleterious variants in KRIT1, CCM2 or PDCD10. In a previous study, we presented the clinical and molecular findings in 140 FCCM individuals. In the present work, we report supporting information on (a) applied diagnostic workflow; (b) clinical significance of molecular findings according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology recommendations; (c) standardization of molecular and clinical data according to the Human Phenotype Ontology; (d) preliminary genotype-phenotype correlations on a subgroup of patients by considering sex, age at diagnosis, neurological symptoms, and number and anatomical site(s) of vascular anomalies; (e) datasets submitted to the Leiden Open Variation Database. An overview of the changes of our diagnostic approach before and after the transition to next-generation sequencing is also reported. This work presents the full procedure that we apply for molecular testing, data interpretation and storing in public databases in FCCM.

Original languageEnglish
Pages (from-to)e24-e36
JournalHuman Mutation
Volume40
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

Keywords

  • CCM2
  • human phenotype ontology
  • KRIT1
  • leiden open variation database
  • mutation
  • PDCD10
  • variant interpretation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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