TY - JOUR
T1 - Mutations in the NKX2-5 gene in patients with stroke and patent foramen ovale
AU - Belvís, Robert
AU - Tizzano, Eduardo F.
AU - Martí-Fàbregas, Joan
AU - Leta, Rubén G.
AU - Baena, Manel
AU - Carreras, Francesc
AU - Pons-Lladó, Guillem
AU - Baiget, Montserrat
AU - Martí-Vilalta, Josep Lluis
PY - 2009/9/1
Y1 - 2009/9/1
N2 - Objective: Patent foramen ovale (PFO) has been related to stroke but its existence has not been explained to date. NKX2-5 is the most implicated gene in fetal atrial septation. We studied NKX2-5 with respect to the presence or absence of PFO in stroke patients. Methods: A prospective analysis of NKX2-5 regarding age, gender, PFO, right-to-left shunt (RLS) size and atrial septal aneurysm (ASA) was performed in consecutive stroke patients and in 50 controls. The entire coding region and intron-exon boundaries of NKX2-5 gene were analyzed by PCR and sequencing of DNA from peripheral lymphocytes. Results: One hundred patients participated in the study (mean age 56.5 ± 12.4 years, 58% males) and PFO was diagnosed in 34% of them by transesophageal echocardiography. RLS was small (12%), moderate (2%) and large (20%). ASA was present in four patients. DNA revealed a novel c.2357G>A change in one PFO patient with cryptogenic stroke. Furthermore, c.182C>T, a mutation previously described in patients with cardiac defects, was detected in two non-PFO women with cryptogenic stroke. None of these changes were detected in our controls. The c.172A>G polymorphism was found in 21% of controls. It appeared more frequently in ASA patients (p = 0.084), in cryptogenic PFO stroke patients (p = 0.097) and in patients with known causes of stroke (p = 0.037). The c.2850C>A polymorphism was also detected in our series with no differences in PFO, RLS size or ASA. Conclusion: Despite the fact that the NKX2-5 could account for the persistence of PFO, mutations of this gene in peripheral blood DNA were barely detected in our study. © 2009 Elsevier B.V. All rights reserved.
AB - Objective: Patent foramen ovale (PFO) has been related to stroke but its existence has not been explained to date. NKX2-5 is the most implicated gene in fetal atrial septation. We studied NKX2-5 with respect to the presence or absence of PFO in stroke patients. Methods: A prospective analysis of NKX2-5 regarding age, gender, PFO, right-to-left shunt (RLS) size and atrial septal aneurysm (ASA) was performed in consecutive stroke patients and in 50 controls. The entire coding region and intron-exon boundaries of NKX2-5 gene were analyzed by PCR and sequencing of DNA from peripheral lymphocytes. Results: One hundred patients participated in the study (mean age 56.5 ± 12.4 years, 58% males) and PFO was diagnosed in 34% of them by transesophageal echocardiography. RLS was small (12%), moderate (2%) and large (20%). ASA was present in four patients. DNA revealed a novel c.2357G>A change in one PFO patient with cryptogenic stroke. Furthermore, c.182C>T, a mutation previously described in patients with cardiac defects, was detected in two non-PFO women with cryptogenic stroke. None of these changes were detected in our controls. The c.172A>G polymorphism was found in 21% of controls. It appeared more frequently in ASA patients (p = 0.084), in cryptogenic PFO stroke patients (p = 0.097) and in patients with known causes of stroke (p = 0.037). The c.2850C>A polymorphism was also detected in our series with no differences in PFO, RLS size or ASA. Conclusion: Despite the fact that the NKX2-5 could account for the persistence of PFO, mutations of this gene in peripheral blood DNA were barely detected in our study. © 2009 Elsevier B.V. All rights reserved.
KW - Cryptogenic
KW - Genetics
KW - NKX2-5
KW - Patent foramen ovale
KW - Stroke
U2 - 10.1016/j.clineuro.2009.04.004
DO - 10.1016/j.clineuro.2009.04.004
M3 - Article
VL - 111
SP - 574
EP - 578
JO - Clinical Neurology and Neurosurgery
JF - Clinical Neurology and Neurosurgery
SN - 0303-8467
IS - 7
ER -