Congenital heart disease is the most frequent form of major birth defects in newbornsaffecting close to 1% of newborn babies (8 per 1,000).The etiology is multifactorial, including a genetic basis (causative genes, orinteractions between genes and environment) and the influence of non-inherited riskfactors (such as multivitamins, maternal illness, drug administration, environmentalagents exposure or also maternal and paternal sociodemographic factors).Heart is considered the first functional organ of the embryo. It develops from themesodermal sheets through the formation of an early linear heart tube which begins tocontract at the eight- to nine-somite stage before the formation of the chambers and theconduction system. Recently, several CHDs have been found to be caused by mutationsof the genes involved in the heart embryogenesis (TFAP2B, Tbx1, NKX2-5, NKX2-6,ZFPM2/FOG2, GATA4). These genes are often investigated as candidate genes if theirbiological role could be associated to the cardiac defect.Genome wide linkage analysis, candidate gene association studies, RNA expressionprofiling and resequencing are commonly used techniques to identify genes responsibleof a certain cardiovascular disorder. The method of analysis can be selected on the basisof the known information about the disease.As a consequence of the increasing number of congenital/genetic cardiovasculardiseases discovered in recent years, the genetic counselling has become very useful toinform the family of the affected subject about the hereditary risk, and to suggest genetictesting for family members.In addition, due to the significant improvement of non invasive imaging techniques(ultrasound imaging) and molecular analysis, prenatal diagnosis is becoming available formany congenital disorders.Chromosomal karyotype with increased band number to identify large chromosomerearrangements, gene or region specific FISH analysis for detecting deletions/insertionsor aneuploidies, indirect PCR assays to assess small gene specific mutations ordeletions/insertions, or direct sequence analysis for the detection of specific pointmutations represent some of the available techniques to detect the disease in an earlyphase. Examples of genetic proved congenital disorders for which a genetic test isavailable are DiGeorge syndrome (deletion 22q11, Tbx1 gene), Williams-Beurensyndrome (microdeletion 7q11.23, gene contiguous syndrome), Alagille syndrome(deletion 20p12, JAG1 gene), Noonan and LEOPARD syndrome (PTPN11, SOS1, KRAS,and RAF-1), Holt-Oram syndrome (mutations in TBX5 gene).© 2012 Nova Science Publishers, Inc. All rights reserved.
State of the heart on genetics of congenital heart diseases: Molecular basis, genetic diagnosis and counselling
Limongelli G.;Calabro P.;
2011
Abstract
Congenital heart disease is the most frequent form of major birth defects in newbornsaffecting close to 1% of newborn babies (8 per 1,000).The etiology is multifactorial, including a genetic basis (causative genes, orinteractions between genes and environment) and the influence of non-inherited riskfactors (such as multivitamins, maternal illness, drug administration, environmentalagents exposure or also maternal and paternal sociodemographic factors).Heart is considered the first functional organ of the embryo. It develops from themesodermal sheets through the formation of an early linear heart tube which begins tocontract at the eight- to nine-somite stage before the formation of the chambers and theconduction system. Recently, several CHDs have been found to be caused by mutationsof the genes involved in the heart embryogenesis (TFAP2B, Tbx1, NKX2-5, NKX2-6,ZFPM2/FOG2, GATA4). These genes are often investigated as candidate genes if theirbiological role could be associated to the cardiac defect.Genome wide linkage analysis, candidate gene association studies, RNA expressionprofiling and resequencing are commonly used techniques to identify genes responsibleof a certain cardiovascular disorder. The method of analysis can be selected on the basisof the known information about the disease.As a consequence of the increasing number of congenital/genetic cardiovasculardiseases discovered in recent years, the genetic counselling has become very useful toinform the family of the affected subject about the hereditary risk, and to suggest genetictesting for family members.In addition, due to the significant improvement of non invasive imaging techniques(ultrasound imaging) and molecular analysis, prenatal diagnosis is becoming available formany congenital disorders.Chromosomal karyotype with increased band number to identify large chromosomerearrangements, gene or region specific FISH analysis for detecting deletions/insertionsor aneuploidies, indirect PCR assays to assess small gene specific mutations ordeletions/insertions, or direct sequence analysis for the detection of specific pointmutations represent some of the available techniques to detect the disease in an earlyphase. Examples of genetic proved congenital disorders for which a genetic test isavailable are DiGeorge syndrome (deletion 22q11, Tbx1 gene), Williams-Beurensyndrome (microdeletion 7q11.23, gene contiguous syndrome), Alagille syndrome(deletion 20p12, JAG1 gene), Noonan and LEOPARD syndrome (PTPN11, SOS1, KRAS,and RAF-1), Holt-Oram syndrome (mutations in TBX5 gene).© 2012 Nova Science Publishers, Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
