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Molecular diagnostic workflow, clinical interpretation of sequence variants, and data repository procedures in 140 individuals with familial cerebral cavernous malformations
Author(s) -
Fusco Carmela,
Copetti Massimiliano,
Mazza Tommaso,
Amoruso Luigi,
Mastroianno Sandra,
Nardella Grazia,
Guarnieri Vito,
Micale Lucia,
D'Agruma Leonardo,
Castori Marco
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23851
Subject(s) - biology , workflow , phenotype , medical genetics , molecular pathology , bioinformatics , genetics , computational biology , pathology , database , medicine , gene , computer science
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.