title: Systematic data-querying of large pediatric biorepository identifies novel Ehlers-Danlos Syndrome variant.
abstract: BACKGROUND
  Ehlers Danlos Syndrome is a rare form of inherited connective tissue disorder, which primarily affects skin, joints, muscle, and blood cells. The current study aimed at finding the mutation that causing EDS type VII C also known as "Dermatosparaxis" in this family.
  
  
  METHODS
  Through systematic data querying of the electronic medical records (EMRs) of over 80,000 individuals, we recently identified an EDS family that indicate an autosomal dominant inheritance. The family was consented for genomic analysis of their de-identified data. After a negative screen for known mutations, we performed whole genome sequencing on the male proband, his affected father, and unaffected mother. We filtered the list of non-synonymous variants that are common between the affected individuals.
  
  
  RESULTS
  The analysis of non-synonymous variants lead to identifying a novel mutation in the ADAMTSL2 (p. Gly421Ser) gene in the affected individuals. Sanger sequencing confirmed the mutation.
  
  
  CONCLUSIONS
  Our work is significant not only because it sheds new light on the pathophysiology of EDS for the affected family and the field at large, but also because it demonstrates the utility of unbiased large-scale clinical recruitment in deciphering the genetic etiology of rare mendelian diseases. With unbiased large-scale clinical recruitment we strive to sequence as many rare mendelian diseases as possible, and this work in EDS serves as a successful proof of concept to that effect.
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Akshatha
authors.initials: A
authors.lastname: Desai
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Connolly
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: March
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Hou
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Rosetta
authors.initials: R
authors.lastname: Chiavacci
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kim
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Gholson
authors.initials: G
authors.lastname: Lyon
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA.
authors.forename: Dexter
authors.initials: D
authors.lastname: Hadley
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, 3615 Civic center Blvd, Philadelphia, PA, 19104, USA. hakonarson@email.chop.edu.|Department of Pediatrics at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. hakonarson@email.chop.edu.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071096:ADAMTS Proteins; D002648:Child; D057225:Data Mining / Q000379:methods*; D030541:Databases, Genetic; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree
chemical_list: D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C000590227:ADAMTSL2 protein, human