title: Bicuspid aortic valve and aortic coarctation are linked to deletion of the X chromosome short arm in Turner syndrome.
abstract: BACKGROUND
  Congenital heart disease (CHD) is a cardinal feature of X chromosome monosomy, or Turner syndrome (TS). Haploinsufficiency for gene(s) located on Xp have been implicated in the short stature characteristic of the syndrome, but the chromosomal region related to the CHD phenotype has not been established.
  
  
  METHODS
  We used cardiac MRI to diagnose cardiovascular abnormalities in four non-mosaic karyotype groups based on 50-metaphase analyses: 45,X (n=152); 46,X,del(Xp) (n=15); 46,X,del(Xq) (n=4); and 46,X,i(Xq) (n=14) from peripheral blood cells.
  
  
  RESULTS
  Bicuspid aortic valves (BAV) were found in 52/152 (34%) 45,X study subjects and aortic coarctation (COA) in 19/152 (12.5%). Isolated anomalous pulmonary veins (APV) were detected in 15/152 (10%) for the 45,X study group, and this defect was not correlated with the presence of BAV or COA. BAVs were present in 28.6% of subjects with Xp deletions and COA in 6.7%. APV were not found in subjects with Xp deletions. The most distal break associated with the BAV/COA trait was at cytologic band Xp11.4 and ChrX:41,500 000. One of 14 subjects (7%) with the 46,X,i(Xq) karyotype had a BAV and no cases of COA or APV were found in this group. No cardiovascular defects were found among four patients with Xq deletions.
  
  
  CONCLUSIONS
  The high prevalence of BAV and COA in subjects missing only the X chromosome short arm indicates that haploinsufficiency for Xp genes contributes to abnormal aortic valve and aortic arch development in TS.
authors.affiliation: Section on Epigenetics and Development, National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bondy
authors.forename: Vladimir K
authors.initials: VK
authors.lastname: Bakalov
authors.forename: Clara
authors.initials: C
authors.lastname: Cheng
authors.forename: Laura
authors.initials: L
authors.lastname: Olivieri
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Rosing
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Arai
mesh_terms: D001017:Aortic Coarctation / Q000209:etiology; D001021:Aortic Valve / Q000002:abnormalities*; D000082882:Bicuspid Aortic Valve Disease; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14; D041321:Chromosomes, Human, X; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D006349:Heart Valve Diseases / Q000209:etiology; D006801:Humans; D059785:Karyotype; D010641:Phenotype; D015995:Prevalence; D011667:Pulmonary Veins / Q000002:abnormalities; D014178:Translocation, Genetic; D014424:Turner Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology*
keywords: Aneuploidy; Chromosomal; Congenital heart disease; Developmental