Abstract
Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124 A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies.
| Original language | English |
|---|---|
| Pages (from-to) | 200-204 |
| Number of pages | 5 |
| Journal | European Journal of Human Genetics |
| Volume | 21 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2013 |
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Keywords
- atrioventricular canal defect
- Noonan syndrome
- PTPN11 gene
- RAF1 gene
- RAS/MAPK pathway
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Atrioventricular canal defect in patients with RASopathies. / Digilio, Maria Cristina; Romana Lepri, Francesca; Lisa Dentici, Maria; Henderson, Alex; Baban, Anwar; Cristina Roberti, Maria; Capolino, Rossella; Versacci, Paolo; Surace, Cecilia; Angioni, Adriano; Tartaglia, Marco; Marino, Bruno; Dallapiccola, Bruno.
In: European Journal of Human Genetics, Vol. 21, No. 2, 02.2013, p. 200-204.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Atrioventricular canal defect in patients with RASopathies
AU - Digilio, Maria Cristina
AU - Romana Lepri, Francesca
AU - Lisa Dentici, Maria
AU - Henderson, Alex
AU - Baban, Anwar
AU - Cristina Roberti, Maria
AU - Capolino, Rossella
AU - Versacci, Paolo
AU - Surace, Cecilia
AU - Angioni, Adriano
AU - Tartaglia, Marco
AU - Marino, Bruno
AU - Dallapiccola, Bruno
PY - 2013/2
Y1 - 2013/2
N2 - Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124 A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies.
AB - Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124 A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies.
KW - atrioventricular canal defect
KW - Noonan syndrome
KW - PTPN11 gene
KW - RAF1 gene
KW - RAS/MAPK pathway
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UR - http://www.scopus.com/inward/citedby.url?scp=84872498338&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2012.145
DO - 10.1038/ejhg.2012.145
M3 - Article
VL - 21
SP - 200
EP - 204
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 2
ER -