XXXX : clinical and molecular findings in 12 newly identified families.

@entity1 @entity64 @entity455 @entity6 @entity40237 @entity63 @entity384 @entity439 @entity33790 @entity413
@entity33790 ( @entity33790 ) is a rare autosomal recessive connective tissue disease, characterized by widespread arterial involvement with elongation, tortuosity, and @entity439 of the large and middle-sized arteries. Recently, @entity40237 mutations were identified in this condition. This gene encodes the @entity413 transporter @entity40237 and was previously suggested as a candidate gene for @entity6 . A total of 12 newly identified @entity33790 families with 16 affected individuals were clinically and molecularly characterized. In addition, extensive cardiovascular imaging and @entity413 tolerance tests were performed in both @entity1 and heterozygous carriers. All 16 @entity1 harbor biallelic @entity40237 mutations of which nine are novel (six missense, three truncating mutations, including a large deletion). Haplotype analysis suggests founder effects for all five recurrent mutations. Remarkably, @entity1 were significantly older than those previously reported in the literature (P=0.04). Only one affected relative died, most likely of an unrelated cause. Although the natural history of @entity33790 in this series was less severe than previously reported, it does indicate a risk for @entity63 events. Two @entity1 initially presented with @entity64 , respectively at age 8 months and 23 years. Tortuosity of the aorta or large arteries was invariably present. Two adult probands (aged 23 and 35 years) had @entity384 , seven @entity1 had localized arterial stenoses, and five had long stenotic stretches of the aorta. Heterozygous carriers did not show any @entity455 . @entity413 metabolism was normal in six @entity1 and eight heterozygous individuals of five families. As such, overt @entity6 is not related to @entity40237 mutations associated with @entity33790 .
