Elastin mutation screening in a group of patients affected by vascular abnormalities.

Supravalvular aortic stenosis is an uncommon but well-characterized congenital form of left ventricular outflow obstruction. The lesion involves the ascending aorta and often occurs in association with pulmonary arterial stenoses or stenoses of other arteries, especially at major branch points. It can occur sporadically, as an autosomal dominant condition, or as one component of Williams-Beuren syndrome. In fact, the clinical and structural characteristics of supravalvular aortic stenosis are identical in both syndromic and nonsyndromic cases. The severity of supravalvular aortic stenosis varies; but if it is left untreated, it may result in heart failure, myocardial infarction, and sudden death. Supravalvular aortic stenosis in Williams-Beuren patients occurs as a consequence of a complete deletion of one copy of the elastin gene on chromosome 7q11.23. However, the underlying genetic cause of isolated supravalvular aortic stenosis has been identified as translations, gross intragenic deletions, and point mutations that disrupt the elastin gene. We report the results obtained in a mutation screening of the elastin gene in 28 patients with supravalvular aortic stenosis and other vascular abnormalities. The aim of the screening was to characterize the molecular cause of this lesion. We have detected 11 changes, including nine polymorphisms and two novel putative missense mutations.

[Congenital heart disease and nuchal translucency with normal karyotype. Report of 3 cases]. / Cardiopathie congénitale et clarté nucale avec caryotype normal. A propos de 3 cas.

We report three pregnancies where enlarged nuchal translucency was discovered at the first trimester transvaginal ultrasound examination; congenital heart disease developed later. Two cases of hypoplastic left heart were diagnosed prenatally at the mid-trimester sonographic examination. The pregnancies were terminated. In the third case, a supravalvular pulmonary stenosis was discovered on the second day of life. Further investigations demonstrated a mutation on the elastin locus, thus confirming the diagnosis of Williams-Beuren syndrome. The role of nuchal translucency as a risk marker for congenital heart disease is discussed.