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

Tom E J Theunissen; Suzanne C E H Sallevelt; Debby M E I Hellebrekers; Bart de Koning; Alexandra T M Hendrickx; Bianca J C van den Bosch; Rick Kamps; Kees Schoonderwoerd; Radek Szklarczyk; Elvira N M Mulder-Den Hartog; Irenaeus F M de Coo; Hubert J M Smeets

doi:10.1016/j.jpeds.2016.12.032

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.

Affiliations

¹ 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.
² Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
³ Department of Clinical Genetics, Erasmus Medical Centre (MC), Rotterdam, The Netherlands.
⁴ Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.
⁵ 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: [email protected].

PMID: 28081892
DOI: 10.1016/j.jpeds.2016.12.032

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