title: Mutations in the NKX2-5 gene in patients with stroke and patent foramen ovale.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Stroke Unit of the Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain. 32353rbn@comb.es
authors.forename: Robert
authors.initials: R
authors.lastname: Belvís
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Tizzano
authors.forename: Joan
authors.initials: J
authors.lastname: Martí-Fàbregas
authors.forename: Rubén G
authors.initials: RG
authors.lastname: Leta
authors.forename: Manel
authors.initials: M
authors.lastname: Baena
authors.forename: Francesc
authors.initials: F
authors.lastname: Carreras
authors.forename: Guillem
authors.initials: G
authors.lastname: Pons-Lladó
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Josep Lluis
authors.initials: JL
authors.lastname: Martí-Vilalta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D004247:DNA / Q000235:genetics; D017548:Echocardiography, Transesophageal; D005091:Exons / Q000235:genetics; D005260:Female; D054092:Foramen Ovale, Patent / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D011446:Prospective Studies; D013030:Spain / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D004247:DNA