Screening of congenital heart disease patients using multiplex ligation-dependent probe amplification: early diagnosis of syndromic patients

TY - JOUR

T1 - Screening of congenital heart disease patients using multiplex ligation-dependent probe amplification

T2 - early diagnosis of syndromic patients

AU - Sørensen, Karina Meden

AU - El-Segaier, Milad

AU - Fernlund, Eva

AU - Errami, Ab

AU - Bouvagnet, Patrice

AU - Nehme, Nancy

AU - Steensberg, Jesper

AU - Hjortdal, Vibeke E.

AU - Soller, Maria

AU - Behjati, Mohaddeseh

AU - Werge, Thomas

AU - Kirchoff, Maria

AU - Schouten, Jan

AU - Tommerup, Niels

AU - Andersen, Paal Skytt

AU - Larsen, Lars Allan

N1 - Copyright © 2012 Wiley Periodicals, Inc.

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

U2 - 10.1002/ajmg.a.35214

DO - 10.1002/ajmg.a.35214

M3 - Journal article

C2 - 22383218

SN - 1552-4825

VL - 158A

SP - 720

EP - 725

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

IS - 4

ER -