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SHR Neuro Cancer Cardio Lipid

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
Web of Science PubMed FullText FullText_MUG


Authors Med Uni Graz:
Gampawar Piyush Gajananrao

Dimensions Citations:

Plum Analytics:
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
Ehlers-Danlos syndrome
hereditary disorders of connective tissue
high-throughput DNA sequencing
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