title: Prospective and Retrospective Diagnosis of Barth Syndrome Aided by Next-Generation Sequencing.
abstract: OBJECTIVE
  To establish a genetic and clinical diagnosis in a newborn with fetal-onset dilated cardiomyopathy using next-generation sequencing technologies.
  
  
  METHODS
  We have conducted the clinical evaluation of the proband and the molecular characterization of his disease by means of whole-exome sequencing. In addition, the clinical evaluation and subsequent genetic screening of five relatives has been performed. This comprises two males with features of left ventricular noncompaction cardiomyopathy, two females suspected of being carriers, and one pregnant female at risk of being a carrier and thereby transmitting the disease to her child.
  
  
  RESULTS
  We have discovered a novel variant in the TAZ gene by means of whole-exome sequencing. This, together with the performance of further clinical analyses, led to an early diagnosis of Barth syndrome in the proband. The genetic screening of the subject's familial group revealed full cosegregation of the variant with another two affected males and identified several female carriers.
  
  
  CONCLUSIONS
  The investigation for Barth syndrome must be considered in male babies and young boys with dilated cardiomyopathy and left ventricular noncompaction. Next-generation sequencing technologies provide an accurate and rapid diagnostic tool in prospectively and retrospectively identifying individuals with this Mendelian syndrome.
authors.affiliation: From the Grupo de Xenética de Enfermidades Cardiovasculares, Instituto de Investigación Sanitaria de Santiago, Red de Investigación Cardiovascular, Fundación Pública Galega de Medicina Xenómica, SERGAS, Santiago de Compostela, Spain maria.brion@usc.es.
authors.forename: María
authors.initials: M
authors.lastname: Brión
authors.affiliation: Department of Pediatrics.
authors.forename: María José
authors.initials: MJ
authors.lastname: de Castro López
authors.affiliation: From the Grupo de Xenética de Enfermidades Cardiovasculares, Instituto de Investigación Sanitaria de Santiago, Red de Investigación Cardiovascular, Fundación Pública Galega de Medicina Xenómica, SERGAS, Santiago de Compostela, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Santori
authors.affiliation: Neonatal Unit, Department of Pediatrics.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pérez Muñuzuri
authors.affiliation: Pediatric Cardiac Unit, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Bernardo
authors.initials: B
authors.lastname: López Abel
authors.affiliation: Neonatal Unit, Department of Pediatrics.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Baña Souto
authors.affiliation: Pediatric Cardiac Unit, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Martínez Soto
authors.affiliation: Neonatal Unit, Department of Pediatrics.
authors.forename: María Luz
authors.initials: ML
authors.lastname: Couce
mesh_terms: D000217:Acyltransferases; D000328:Adult; D056889:Barth Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D010375:Pedigree; D011446:Prospective Studies; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014157:Transcription Factors; D000217:Acyltransferases; C108675:TAFAZZIN protein, human
keywords: Barth syndrome; Dilated cardiomyopathy; Early diagnosis; Left ventricular noncompaction; Neutropenia; Next-generation sequencing