title: Screening of congenital heart disease patients using multiplex ligation-dependent probe amplification: early diagnosis of syndromic patients.
abstract: Recurrent copy number variants (CNVs) are found in a significant proportion of patients with congenital heart disease (CHD) and some of these CNVs are associated with other developmental defects. In some syndromic patients, CHD may be the first presenting symptom, thus screening of patients with CHD for CNVs in specific genomic regions may lead to early diagnosis and awareness of extracardiac symptoms. We designed a multiplex ligation-dependent probe amplification (MLPA) assay specifically for screening of CHD patients. The MLPA assay allows for simultaneous analysis of CNVs in 25 genomic regions previously associated with CHD. We screened blood samples from 402 CHD patients and identified 14 rare CNVs in 13 (3.2%) patients. Five CNVs were de novo and six where inherited from a healthy parent. The MLPA screen led to early syndrome diagnosis in two of these patients. We conclude that the MLPA assay detects clinically relevant CNVs and suggest that it could be used within pediatric cardiology as a first tier screen to detect clinically relevant CNVs and identify syndromic patients at an early stage.
authors.affiliation: Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Karina Meden
authors.initials: KM
authors.lastname: Sørensen
authors.forename: Milad
authors.initials: M
authors.lastname: El-Segaier
authors.forename: Eva
authors.initials: E
authors.lastname: Fernlund
authors.forename: Ab
authors.initials: A
authors.lastname: Errami
authors.forename: Patrice
authors.initials: P
authors.lastname: Bouvagnet
authors.forename: Nancy
authors.initials: N
authors.lastname: Nehme
authors.forename: Jesper
authors.initials: J
authors.lastname: Steensberg
authors.forename: Vibeke
authors.initials: V
authors.lastname: Hjortdal
authors.forename: Maria
authors.initials: M
authors.lastname: Soller
authors.forename: Mohaddeseh
authors.initials: M
authors.lastname: Behjati
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Maria
authors.initials: M
authors.lastname: Kirchoff
authors.forename: Jan
authors.initials: J
authors.lastname: Schouten
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
authors.forename: Paal Skytt
authors.initials: PS
authors.lastname: Andersen
authors.forename: Lars Allan
authors.initials: LA
authors.lastname: Larsen
mesh_terms: D000293:Adolescent; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics*; D006331:Heart Diseases / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods; D021141:Nucleic Acid Amplification Techniques