Systemic Screening for 22q11.2 Copy Number Variations in Hungarian Pediatric and Adult Patients With Congenital Heart Diseases Identified Rare Pathogenic Patterns in the Region.

Congenital heart defects (CHD) are the most common developmental abnormalities, affecting approximately 0.9% of livebirths. Genetic factors, including copy number variations (CNVs), play an important role in their development. The most common CNVs are found on chromosome 22q11.2. The genomic instability of this region, caused by the eight low copy repeats (LCR A-H), may result in several recurrent and/or rare microdeletions and duplications, including the most common, ∼3 Mb large LCR A-D deletion (classical 22q.11.2 deletion syndrome). We aimed to screen 22q11.2 CNVs in a large Hungarian pediatric and adult CHD cohort, regardless of the type of their CHDs. All the enrolled participants were cardiologically diagnosed with non-syndromic CHDs. A combination of multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis and droplet digital PCR methods were used to comprehensively assess the detected 22q11.2 CNVs in 212 CHD-patients. Additionally, capillary sequencing was performed to detect variants in the TBX1 gene, a cardinal gene located in 22q11.2. Pathogenic CNVs were detected in 5.2% (11/212), VUS in 0.9% and benign CNVs in 1.8% of the overall CHD cohort. In patients with tetralogy of Fallot the rate of pathogenic CNVs was 17% (5/30). Fifty-four percent of all CNVs were typical proximal deletions (LCR A-D). However, nested (LCR A-B) and central deletions (LCR C-D), proximal (LCR A-D) and distal duplications (LCR D-E, LCR D-H, LCR E-H, LCR F-H) and rare combinations of deletions and duplications were also identified. Segregation analysis detected familial occurrence in 18% (2/11) of the pathogenic variants. Based on in-depth clinical information, a detailed phenotype-genotype comparison was performed. No pathogenic variant was identified in the TBX1 gene. Our findings confirmed the previously described large phenotypic diversity in the 22q11.2 CNVs. MLPA proved to be a highly efficient genetic screening method for our CHD-cohort. Our results highlight the necessity for large-scale genetic screening of CHD-patients and the importance of early genetic diagnosis in their clinical management.

Volumetric and functional assessment of the left atrium in young competitive athletes without left ventricular hypertrophy: the MAGYAR-Sport Study.

BACKGROUND: Left atrial (LA) remodeling may be regarded as a physiologic adaptation to exercise conditioning. Three-dimensional speckle tracking echocardiography (3DSTE) is a new promising tool for volumetric and functional characterization of the LA. The present study was undertaken to assess adaptive changes in LA volumes and functional properties respecting cardiac cycle in young competitive athletes without left ventricular hypertrophy (LVH) by detailed 3DSTE assessment. METHODS: The study group consisted of 20 young elite basketball and handball players (mean age: 28.1±10.1 years, 8 men) without LVH, their results were compared to 23 age- and gender-matched non-sportive healthy controls (mean age: 31.7±8.5 years, 11 men. All subjects had undergone standard transthoracic two-dimensional Doppler echocardiographic study with 3DSTE. RESULTS: Increased systolic maximum (66.5±13.6 mL vs. 38.5±8.6 mL, P<0.0001) and diastolic minimum (36.7±8.1 mL vs. 17.5±5.8 mL, P<0.0001) and preatrial contraction (46.2±10.1 mL vs. 26.2±7.8 mL, P<0.0001) LA volumes could be demonstrated in athletes. Total (29.7±9.0 mL vs. 20.7±5.0 mL, P=0.0002) and passive LA stroke volumes (19.8±8.7 mL vs. 12.4±4.6 mL, P=0.0009) were increased, while total (44.2±9.1 mL vs. 54.2±9.4 mL, P=0.001) and active LA emptying fractions (20.6±11.8% vs. 31.9±8.7%, P=0.0008) proved to be decreased in athletes as compared to controls. Active LA stroke volume (9.9±5.8 mL vs. 8.3±3.3 mL, P=0.29) and passive LA emptying fraction (29.1±10.6 mL vs. 32.6±11.2 mL, P=0.31) did not differ between the groups. Only circumferential global (21.1±7.7% vs. 27.6±9.9%, P=0.02) and mean segmental (26.1±7.1% vs. 35.7±12.0%, P=0.003) peak LA strains proved to be significantly reduced in athletes as compared to controls. CONCLUSIONS: 3DSTE-derived increased cyclic LA volumes and specific alterations in LA functional properties could be demonstrated in young competing athletes which is most likely a physiologic consequence of a global cardiac adaptation to intensive and chronic training.

Right atrial deformation analysis in isolated left ventricular noncompaction - insights from the three-dimensional speckle tracking echocardiographic MAGYAR-Path Study.

OBJECTIVE: Isolated left ventricular noncompaction (ILVNC) is a rare cardiomyopathy characterized by a prominent trabecular meshwork and deep intertrabecular recesses. The present study aimed to examine right atrial (RA) volumes, volume-based functional properties and strains by three-dimensional speckle-tracking echocardiography (3DSTE) in ILVNC patients. METHODS: The study group consisted of 13 patients with ILVNC (mean age: 54.6±14.1 years, six male) and 23 healthy age- and gender-matched volunteers (mean age: 50.4±12.4 years, 10 male), who served as normal controls. Complete two-dimensional Doppler echocardiography and 3DSTE were performed in all cases. RESULTS: Increased systolic maximum (58.2±15.3 ml vs. 40.5±11.8 ml, p=0.0004) and diastolic pre-atrial contraction (39.6±16.1 ml vs. 28.2±9.2 ml, p=0.01) and minimum (46.2±17.5 ml vs. 34.6±11.6 ml, p=0.02) RA volumes were detected in ILVNC patients. Only total (18.6±8.5 ml vs. 12.2±5.9 ml, p=0.01) and passive (12.0±13.3 vs. 5.9±3.7 ml, p=0.05) RA stroke volumes, representing features of RA reservoir and conduit phases, were increased in ILVNC; active RA stroke volume and all emptying fractions did not differ between ILVNC patients and matched controls. Moreover, global, mean segmental and regional peak strains and strains at atrial contraction showed no differences between ILVNC patients and controls. CONCLUSIONS: 3DSTE-derived volumetric analysis confirmed increased cyclic RA volumes in ILVNC. Only mild RA functional alterations were demonstrated in ILVNC.