Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Weerakkody, RA; Vandrovcova, J; Kanonidou, C; Mueller, M; Gampawar, P; Ibrahim, Y; Norsworthy, P; Biggs, J; Abdullah, A; Ross, D; Black, HA; Ferguson, D; Cheshire, NJ; Kazkaz, H; Grahame, R; Ghali, N; Vandersteen, A; Pope, FM; Aitman, TJ.
Targeted next-generation sequencing makes new molecular diagnoses and expands genotype-phenotype relationship in Ehlers-Danlos syndrome.
Genet Med. 2016; 18(11):1119-1127
Doi: 10.1038/gim.2016.14
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- Co-Autor*innen der Med Uni Graz
- Gampawar Piyush Gajananrao
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- Abstract:
- Ehlers-Danlos syndrome (EDS) comprises a group of overlapping hereditary disorders of connective tissue with significant morbidity and mortality, including major vascular complications. We sought to identify the diagnostic utility of a next-generation sequencing (NGS) panel in a mixed EDS cohort. We developed and applied PCR-based NGS assays for targeted, unbiased sequencing of 12 collagen and aortopathy genes to a cohort of 177 unrelated EDS patients. Variants were scored blind to previous genetic testing and then compared with results of previous Sanger sequencing. Twenty-eight pathogenic variants in COL5A1/2, COL3A1, FBN1, and COL1A1 and four likely pathogenic variants in COL1A1, TGFBR1/2, and SMAD3 were identified by the NGS assays. These included all previously detected single-nucleotide and other short pathogenic variants in these genes, and seven newly detected pathogenic or likely pathogenic variants leading to clinically significant diagnostic revisions. Twenty-two variants of uncertain significance were identified, seven of which were in aortopathy genes and required clinical follow-up. Unbiased NGS-based sequencing made new molecular diagnoses outside the expected EDS genotype-phenotype relationship and identified previously undetected clinically actionable variants in aortopathy susceptibility genes. These data may be of value in guiding future clinical pathways for genetic diagnosis in EDS.Genet Med 18 11, 1119-1127.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Child -
- Child, Preschool -
- Collagen - genetics
- Ehlers-Danlos Syndrome - diagnosis
- Ehlers-Danlos Syndrome - genetics
- Ehlers-Danlos Syndrome - physiopathology
- Female -
- Genetic Testing -
- Genotype -
- High-Throughput Nucleotide Sequencing - methods
- Humans -
- Male -
- Middle Aged -
- Mutation - genetics
- Pathology, Molecular - methods
- Phenotype -
- Protein-Serine-Threonine Kinases - genetics
- Receptor, Transforming Growth Factor-beta Type I -
- Receptors, Transforming Growth Factor beta - genetics
- Young Adult -
- Find related publications in this database (Keywords)
- aortic disease
- collagen
- Ehlers-Danlos syndrome
- hereditary disorders of connective tissue
- high-throughput DNA sequencing