20 research outputs found
ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype
Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity. Three novel loss of function (LoF) variants were identified in six patients from three families. Clinically, all patients presented anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. Three patients had (recurrent) subaortic membrane, suggesting that ADAMTS19 is the first gene identified related to discrete subaortic stenosis. One case presented a bi-commissural pulmonary valve. All patients displayed some degree of atrioventricular valve insufficiency. Other cardiac anomalies included atrial/ventricular septal defects, persistent ductus arteriosus, and mild dilated ascending aorta. Our findings confirm that biallelic LoF variants in ADAMTS19 are causative of a specific and recognizable cardiac phenotype. We recommend considering ADAMTS19 genetic testing in all patients with multiple semilunar valve abnormalities, particularly in the presence of subaortic membrane. ADAMTS19 screening in patients with semilunar valve abnormalities is needed to estimate the frequency of the HVD related phenotype, which might be not so rare
ΠΠΎΡΡΠ΅ΠΊΡΠΈΡ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»ΡΠ½ΡΡ ΠΈ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΡΠ΅ΡΠΊΠΈΡ ΡΡΠ½ΠΊΡΠΈΠΉ Π² Π»Π΅ΡΠ΅Π½ΠΈΠΈ ΠΈ ΡΠ΅Π°Π±ΠΈΠ»ΠΈΡΠ°ΡΠΈΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ ΡΠΈΠ·ΠΎΡΠΈΠΏΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠ°ΡΡΡΡΠΎΠΉΡΡΠ²ΠΎΠΌ
ΠΠ° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ Π½Π΅Π²Π΅ΡΠ±Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΠΈΠ·ΠΎΡΠΈΠΏΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠ°ΡΡΡΡΠΎΠΉΡΡΠ²ΠΎΠΌ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Ρ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ, ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΊΠΎΡΠΎΡΡΡ
Π² ΠΈΡ
ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ Π΄ΠΎΠ±ΠΈΡΡΡΡ Π±ΠΎΠ»Π΅Π΅ ΠΏΠΎΠ»Π½ΠΎΠΉ ΡΠ΅Π΄ΡΠΊΡΠΈΠΈ ΠΏΡΠΈΡ
ΠΎΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΈΠΌΠΏΡΠΎΠΌΠ°ΡΠΈΠΊΠΈ.Behavioral methods were worked out basing of the peculiarities of nonβverbal behavior of the patients with schizotypical disorders. The use of the methods in complex therapy allows to achieve more complete reduction in psychopathological signs
Assessment of ventricular septal defect closure by intraoperative epicardial ultrasound
Intraoperative epicardial two-dimensional echocardiographic imaging, color flow mapping and contrast echocardiography were used in 31 patients after patch closure of a ventricular septal defect to determine their respective values in the assessment of residual shunting after cardiopulmonary bypass and for the prediction of long-term results. Epicardial imaging showed no incidence of patch dehiscence. Residual shunting detected by color flow mapping or contrast echocardiography was graded into one of four categories (0 to III). Real time analysis of color flow mapping studies suggested no shunting (grade 0) in 2 patients, grade I shunting in 20, grade II in 8 and grade III in 1; contrast studies suggested grade 0 in 15, grade I in 6, grade II in 8 and grade III in 2. Interobserver variation in real time encoding of grade I or II shunting was 25% by color flow mapping and 6% by contrast echocardiography. Subsequent frame by frame analysis revealed that both diastolic and early systolic right ventricular turbulence gave rise to false positive results during real time analysis of color flow mapping studies. Color flow mapping allowed exact localization of residual shunting, whereas contrast echocardiography allowed better semiquantification. Postbypass results were correlated in 30 patients with late postoperative precordial studies (mean interval 7.5 months). Persistent shunts were found in 6 (20%) of 30 patients. No patient required reoperation for residual shunting. The predictive value of immediate grade I or II shunting as a marker for persistent long-term shunting was poor, whereas both patients with immediate grade III shunting had shunt persistence, indicating that immediate revision should be considered in such patients. Intraoperative epicardial ultrasound is valuable for the immediate exclusion of important residual shunting after ventricular septal defect closure. Maximal information is obtained when color flow mapping and contrast echocardiography are used in combination
Autosomal dominant inheritance of left ventricular outflow tract obstruction
Most nonsyndromic congenital heart malformations (CHMs) in humans are multifactorial in origin, although an increasing number of monogenic cases have been reported recently. We describe here four new families with presumed autosomal dominant inheritance of left ventricular outflow tract obstruction (LVOTO), consisting of hypoplastic left heart (HLHS) or left ventricle (HLV), aortic valve stenosis (AS) and bicuspid aortic valve (BAV), hypoplastic aortic arch (HAA), and coarctation of the aorta (CoA). LVOTO in these families shows a wide clinical spectrum with some family members having severe anomalies such as hypoplastic left heart, and others only minor anomalies such as mild aortic valve stenosis. This supports the suggestion that all anomalies of the LVOTO spectrum are developmentally related and can be caused by a single gene defect