X chromosome monosomy restricted to the left ventricle is not a major cause of isolated hypoplastic left heart

Hypoplastic left heart sequence (HLHS) encompasses obstructive lesions of the left side of the heart accompanied by varying degrees of underdevelopment of the mitral valve, either atresia or stenosis, left ventricle, aortic valve, and ascending aorta. HLHS has an incidence of 0.016-0.036% live births and can occur as an isolated defect or several different chromosome abnormalities. In particular, about 20% of patients with monosomy X, have HLHS, suggesting a relationship between this form of aneuploidy and this congenital heart defect (CHD). Somatic mutations restricted to the cardiac affected structure have been considered a mechanism of CHD. The aim of this study was to evaluate if monosomy X restricted to the left ventricle causes isolated HLHS. Formalin-fixed, paraffin-embedded cardiac tissue obtained from 19 patients with HLHS (10 males and 9 females) without extra cardiac anomalies and with a normal constitutional karyotype, were investigated by FISH analysis, using X/Y/18 centromeric probes. The results of this analysis were compared with those obtained by examining the heart specimens of 15 chromosomally normal pediatric patients affected by either restrictive or dilated cardiomyopathy, which were used as negative controls. Mosaic monosomy X was detected in the cardiac tissue nuclei of both groups, with similar frequencies (6-16% and 12-16%, respectively), suggesting that chromosome X monosomy is not rare in this tissue, but is not a major cause of isolated HLHS.