title: A Case of HDR Syndrome and Ichthyosis: Dual Diagnosis by Whole-Genome Sequencing of Novel Mutations in GATA3 and STS Genes.
abstract: BACKGROUND
  Atypical presentations of complex multisystem disorders may elude diagnosis based on clinical findings only. Appropriate diagnostic tests may not be available or available tests may not provide appropriate coverage of relevant genomic regions for patients with complex phenotypes. Clinical whole-exome/-genome sequencing is often considered for complex patients lacking a definitive diagnosis.
  
  
  METHODS
  A boy who is now 7 years old presented as a newborn with congenital ichthyosis. At 6 weeks of age, he presented with failure to thrive and hypoparathyroidism. At 4 years of age, he was diagnosed with sensorineural hearing loss. Whole-genome sequencing identified novel mutations in GATA3, which causes HDR syndrome (hypoparathyroidism and deafness), and STS, which causes X -linked congenital ichthyosis.
  
  
  CONCLUSIONS
  Whole-genome sequencing led to a definitive clinical diagnosis in a case where no other clinical test was available for GATA3, and no sequencing panel would have included both genes because they have disparate phenotypes. This case demonstrates the power of whole-genome (or exome) sequencing for patients with complex clinical presentations involving endocrine abnormalities.
authors.affiliation: Division of Endocrinology, Department of Pediatrics (G.G.), and Division of Genetics and Genomics (P.P.H., D.T.M.), Children's Hospital of Boston, Boston, Massachusetts 02115.
authors.forename: Gregory
authors.initials: G
authors.lastname: Goodwin
authors.affiliation: Division of Endocrinology, Department of Pediatrics (G.G.), and Division of Genetics and Genomics (P.P.H., D.T.M.), Children's Hospital of Boston, Boston, Massachusetts 02115.
authors.forename: Pamela P
authors.initials: PP
authors.lastname: Hawley
authors.affiliation: Division of Endocrinology, Department of Pediatrics (G.G.), and Division of Genetics and Genomics (P.P.H., D.T.M.), Children's Hospital of Boston, Boston, Massachusetts 02115.
authors.forename: David T
authors.initials: DT
authors.lastname: Miller
mesh_terms: D002648:Child; D059472:Exome; D050990:GATA3 Transcription Factor / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007011:Hypoparathyroidism / Q000175:diagnosis / Q000235:genetics*; D007057:Ichthyosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D009401:Nephrosis / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D043266:Steryl-Sulfatase / Q000235:genetics*
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C584039:STS protein, human; D043266:Steryl-Sulfatase