Identification of dosage-sensitive genes in fetuses referred with severe isolated congenital diaphragmatic hernia

P D Brady; P DeKoninck; J P Fryns; K Devriendt; J A Deprest; J R Vermeesch

doi:10.1002/pd.4244

Identification of dosage-sensitive genes in fetuses referred with severe isolated congenital diaphragmatic hernia

P D Brady, P DeKoninck, J P Fryns, K Devriendt, J A Deprest, J R Vermeesch

Research output: Contribution to journal › Article › Academic › peer-review

37 Citations (Scopus)

Abstract

OBJECTIVE:
Congenital diaphragmatic hernia (CDH) is a fetal abnormality affecting diaphragm and lung development with a high mortality rate despite advances in fetal and neonatal therapy. CDH may occur either as an isolated defect or in syndromic form for which the prognosis is worse. Although conventional karyotyping and, more recently, chromosomal microarrays support a substantial role for genetic factors, causal genes responsible for isolated CDH remain elusive. We propose that chromosomal microarray analysis will identify copy number variations (CNVs) associated with isolated CDH.

METHODS:
We perform a prospective genome-wide screen for CNVs using chromosomal microarrays on 75 fetuses referred with apparently isolated CDH, six of which were later reclassified as non-isolated CDH.

RESULTS:
The results pinpoint haploinsufficiency of NR2F2 as a cause of CDH and cardiovascular malformations. In addition, the 15q25.2 and 16p11.2 recurrent microdeletions are associated with isolated CDH. By using gene prioritisation and network analysis, we provide strong evidence for several novel dosage-sensitive candidate genes associated with CDH.

CONCLUSIONS:
Chromosomal microarray analysis detects submicroscopic CNVs associated with isolated CDH or CDH with cardiovascular malformations.

Original language	English
Pages (from-to)	1283-92
Number of pages	10
Journal	Prenatal Diagnosis
Volume	33
Issue number	13
DOIs	https://doi.org/10.1002/pd.4244
Publication status	Published - Dec 2013
Externally published	Yes

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@article{f4fd3e8b52064bb79a18f22aebb9220f,

title = "Identification of dosage-sensitive genes in fetuses referred with severe isolated congenital diaphragmatic hernia",

abstract = "OBJECTIVE: Congenital diaphragmatic hernia (CDH) is a fetal abnormality affecting diaphragm and lung development with a high mortality rate despite advances in fetal and neonatal therapy. CDH may occur either as an isolated defect or in syndromic form for which the prognosis is worse. Although conventional karyotyping and, more recently, chromosomal microarrays support a substantial role for genetic factors, causal genes responsible for isolated CDH remain elusive. We propose that chromosomal microarray analysis will identify copy number variations (CNVs) associated with isolated CDH.METHODS: We perform a prospective genome-wide screen for CNVs using chromosomal microarrays on 75 fetuses referred with apparently isolated CDH, six of which were later reclassified as non-isolated CDH.RESULTS:The results pinpoint haploinsufficiency of NR2F2 as a cause of CDH and cardiovascular malformations. In addition, the 15q25.2 and 16p11.2 recurrent microdeletions are associated with isolated CDH. By using gene prioritisation and network analysis, we provide strong evidence for several novel dosage-sensitive candidate genes associated with CDH.CONCLUSIONS: Chromosomal microarray analysis detects submicroscopic CNVs associated with isolated CDH or CDH with cardiovascular malformations.",

author = "Brady, {P D} and P DeKoninck and Fryns, {J P} and K Devriendt and Deprest, {J A} and Vermeesch, {J R}",

note = "{\textcopyright} 2013 John Wiley & Sons, Ltd.",

year = "2013",

month = dec,

doi = "10.1002/pd.4244",

language = "English",

volume = "33",

pages = "1283--92",

journal = "Prenatal Diagnosis",

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TY - JOUR

T1 - Identification of dosage-sensitive genes in fetuses referred with severe isolated congenital diaphragmatic hernia

AU - Brady, P D

AU - DeKoninck, P

AU - Fryns, J P

AU - Devriendt, K

AU - Deprest, J A

AU - Vermeesch, J R

PY - 2013/12

Y1 - 2013/12

N2 - OBJECTIVE: Congenital diaphragmatic hernia (CDH) is a fetal abnormality affecting diaphragm and lung development with a high mortality rate despite advances in fetal and neonatal therapy. CDH may occur either as an isolated defect or in syndromic form for which the prognosis is worse. Although conventional karyotyping and, more recently, chromosomal microarrays support a substantial role for genetic factors, causal genes responsible for isolated CDH remain elusive. We propose that chromosomal microarray analysis will identify copy number variations (CNVs) associated with isolated CDH.METHODS: We perform a prospective genome-wide screen for CNVs using chromosomal microarrays on 75 fetuses referred with apparently isolated CDH, six of which were later reclassified as non-isolated CDH.RESULTS:The results pinpoint haploinsufficiency of NR2F2 as a cause of CDH and cardiovascular malformations. In addition, the 15q25.2 and 16p11.2 recurrent microdeletions are associated with isolated CDH. By using gene prioritisation and network analysis, we provide strong evidence for several novel dosage-sensitive candidate genes associated with CDH.CONCLUSIONS: Chromosomal microarray analysis detects submicroscopic CNVs associated with isolated CDH or CDH with cardiovascular malformations.

AB - OBJECTIVE: Congenital diaphragmatic hernia (CDH) is a fetal abnormality affecting diaphragm and lung development with a high mortality rate despite advances in fetal and neonatal therapy. CDH may occur either as an isolated defect or in syndromic form for which the prognosis is worse. Although conventional karyotyping and, more recently, chromosomal microarrays support a substantial role for genetic factors, causal genes responsible for isolated CDH remain elusive. We propose that chromosomal microarray analysis will identify copy number variations (CNVs) associated with isolated CDH.METHODS: We perform a prospective genome-wide screen for CNVs using chromosomal microarrays on 75 fetuses referred with apparently isolated CDH, six of which were later reclassified as non-isolated CDH.RESULTS:The results pinpoint haploinsufficiency of NR2F2 as a cause of CDH and cardiovascular malformations. In addition, the 15q25.2 and 16p11.2 recurrent microdeletions are associated with isolated CDH. By using gene prioritisation and network analysis, we provide strong evidence for several novel dosage-sensitive candidate genes associated with CDH.CONCLUSIONS: Chromosomal microarray analysis detects submicroscopic CNVs associated with isolated CDH or CDH with cardiovascular malformations.

U2 - 10.1002/pd.4244

DO - 10.1002/pd.4244

M3 - Article

C2 - 24122781

SN - 0197-3851

VL - 33

SP - 1283

EP - 1292

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 13

ER -

Identification of dosage-sensitive genes in fetuses referred with severe isolated congenital diaphragmatic hernia

Abstract

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