title: Rapid Resolution of Blended or Composite Multigenic Disease in Infants by Whole-Exome Sequencing.
abstract: Whole-exome sequencing identified multiple genetic causes in 2 infants with heterogeneous disease. Three gene defects in the first patient explained all symptoms, but manifestations were overlapping (blended phenotype). Two gene defects in the second patient explained nonoverlapping symptoms (composite phenotype). Whole-exome sequencing rapidly and comprehensively resolves heterogeneous genetic disease.
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Genetics and Cell Biology, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Tom E J
authors.initials: TEJ
authors.lastname: Theunissen
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Suzanne C E H
authors.initials: SCEH
authors.lastname: Sallevelt
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Debby M E I
authors.initials: DMEI
authors.lastname: Hellebrekers
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: de Koning
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Alexandra T M
authors.initials: ATM
authors.lastname: Hendrickx
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Bianca J C
authors.initials: BJC
authors.lastname: van den Bosch
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Kamps
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Centre (MC), Rotterdam, The Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Schoonderwoerd
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Radek
authors.initials: R
authors.lastname: Szklarczyk
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Elvira N M
authors.initials: ENM
authors.lastname: Mulder-Den Hartog
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Irenaeus F M
authors.initials: IFM
authors.lastname: de Coo
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Genetics and Cell Biology, School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: bert.smeets@maastrichtuniversity.nl.
authors.forename: Hubert J M
authors.initials: HJM
authors.lastname: Smeets
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D000013:Congenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D059472:Exome / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000175:diagnosis*; D005820:Genetic Testing / Q000379:methods; D023281:Genomics; D005838:Genotype; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins; D009152:Mutagenicity Tests; D009154:Mutation; D010641:Phenotype; D018000:Receptors, Peptide / Q000235:genetics; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D012720:Severity of Illness Index
chemical_list: C447150:ANTXR2 protein, human; C561542:BICD2 protein, human; C102160:HPS1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D018000:Receptors, Peptide; D002265:Carboxylic Ester Hydrolases; C576043:SERAC1 protein, human; D000581:Amidohydrolases; C019672:aminoacylase I
keywords: complex disease; genetic diagnosis; phenotypic characterization