Molecular characterization of 22q11 deletion in a three-generation family with maternal transmission.

Haploinsufficiency of chromosome 22q11.2 is a well-established cause of both the DiGeorge anomaly and the velocardiofacial syndrome. This condition shows a continuous spectrum of phenotypic manifestations with a considerable inter- and intrafamilial variability. We report on a three-generation family with four members sharing the same 3 Mb long deletion but showing different phenotypic expression. In the first generation, the deleted patient has hypernasal speech and suffers from recurrent psychotic episodes. Two of her offspring inherited the deletion. One of these, a male, has hypernasal speech, low-set ears, hypocalcemia, severe development delay, and tetralogy of Fallot. The other, a female, has hypernasal speech, minor facial anomalies, and very mild mental retardation. Her daughter has tetralogy of Fallot, velopharyngeal insufficiency, and mild facial anomalies. This family is an example of the widely variable phenotypic expressivity of the 22q11.2 deletion. There is no correlation between the size of the deletion and the phenotypic manifestations. Genetic background and/or environmental factors could explain the different phenotypes observed in the affected members of the family.

Implantation of an elastic ring at equator of the left ventricle influences cardiac mechanics in experimental acute ventricular dysfunction.

OBJECTIVES: We hypothesize that the implantation of an endoventricular elastic ring at the left ventricle (LV) equatorial site will positively affect the cardiac mechanics in an experimental model of acute LV dysfunction. BACKGROUND: Changes in the elastic properties of LV occur in the dilated and failing heart, contributing to overall cardiac mechanical dysfunction. No interventions are as yet specifically designed to improve LV elasticity in failing hearts. METHODS: Acute LV enlargement and dysfunction was induced in 13 healthy sheep via the insertion of a large Dacron patch into the lateral wall. In 6 of these sheep, a customized elastic ring was implanted at the inner surface of the LV equator (ring group), and the remaining 7 served as control subjects (dysfunction group). Systolic and diastolic function was evaluated using echocardiography and pressure-volume (P-V) analysis. RESULTS: In the ring group, both the maximum rate of pressure increase and the slope of end-systolic P-V relationship were significantly different from those without ring (1,718 +/- 726 vs. 1,049 +/- 269 and 1.25 +/- 0.30 vs. 0.88 +/- 0.19; both p < 0.05). Preload recruitable stroke work changed even more prominently (33 +/- 11 vs. 17 +/- 5; p = 0.005), along with stroke volume, ejection fraction, and stroke work. Although ring implantation had no effect on end-diastolic P-V relationship, it positively affected the active component of diastole: the maximum rate of pressure decrease declined significantly (p = 0.037). The time constant of relaxation tended to decrease (37 +/- 8 vs. 44 +/- 6; p = 0.088). CONCLUSIONS: Improving the elastic component of the LV at its equatorial site substantially augments contractility and early relaxation in acute systodiastolic LV dysfunction.

The Titan can help titin: from micro to macro myocardial elasticity.

Heart failure of different etiologies is due to changes in cardiac structure and function. During normal diastolic filling, the passive stretch of the ventricular myocardium is modulated by titin, a giant elastic protein that acts as a molecular spring and leads to the recapitulation of single cell mechanics at global ventricular level. The mechanics of a dilated failing heart are at least partially determined by variations in the passive filling properties of the myocardium that impair contraction. Current volume reduction surgery is based on Laplace's law and obtained by rigid means that may impair diastolic function. We postulate that inserting one or more elastic elements at different levels of a failing ventricle (the mitral annulus, equator and apex) could improve cardiac performance. We describe our invention for the first time by presenting the results of two animal experiments.

Association between 5,10-methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and conotruncal heart defects.

Reports related some polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) to folate-dependent neural tube defects. In view of the common origin of the cells involved both in neural tube closure and heart septation, we analyzed the MTHFR C677T and A1298C polymorphisms in mothers of children with conotruncal heart defect (CD) and in their offspring to evaluate the association between the MTHFR genotype and the risk of CD. We genotyped 103 Italian mothers with CD offspring, 200 control mothers, 103 affected children and their fathers by restriction fragment length polymorphism analysis. No increased risk was observed for the prevalence of the 677TT genotype by itself in affected children and in their mothers. The combined maternal 677TT/1298AA and 677CC/1298CC genotypes have odds ratio of 1.73 and 1.85, respectively. The prevalence of 1298CC genotype in the affected children gives odds ratio of 1.90, that becomes 2.31 for the 677CC/1298CC genotype. However, none of the odds ratios was statistically significant. We observed a higher frequency of the 677T allele in Italy than in other European countries. No association has been demonstrated between the 677TT MTHFR genotype and CD.