Rapid Resolution of Blended or Composite Multigenic Disease in Infants by Whole-Exome Sequencing

J Pediatr. 2017 Mar:182:371-374.e2. doi: 10.1016/j.jpeds.2016.12.032. Epub 2017 Jan 9.

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.

Keywords: complex disease; genetic diagnosis; phenotypic characterization.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / genetics
  • Carboxylic Ester Hydrolases / genetics
  • Congenital Abnormalities / diagnosis
  • Congenital Abnormalities / genetics*
  • Exome / genetics
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Testing / methods
  • Genomics
  • Genotype
  • Humans
  • Infant
  • Membrane Proteins / genetics
  • Microtubule-Associated Proteins
  • Mutagenicity Tests
  • Mutation*
  • Phenotype
  • Receptors, Peptide / genetics
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods*
  • Severity of Illness Index

Substances

  • ANTXR2 protein, human
  • BICD2 protein, human
  • HPS1 protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Receptors, Peptide
  • Carboxylic Ester Hydrolases
  • SERAC1 protein, human
  • Amidohydrolases
  • aminoacylase I