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Cristina Basso

Publications and source records attributed to Cristina Basso.

At least 37 records · Page 2Linked to original sources
PubMed2005

Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1.

OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous disorder characterized by fibro-fatty replacement of the right ventricular myocardium, associated with high risk of sudden death. The objective of this study is to identify the gene involved in ARVD1, which has been elusive ever since its locus was mapped to chromosome 14q24.3. METHODS AND RESULTS: Mutation screening of the promoter and untranslated regions (UTRs) of the transforming growth factor-beta3 (TGFbeta3) gene was performed by direct sequencing of genomic DNA of one index case belonging to an ARVD1 family including 38 members in four generations. We detected a nucleotide substitution (c.-36G>A) in 5' UTR of TGFbeta3 gene, invariably associated with the typical ARVC clinical phenotype in the affected family members, according to the established diagnostic criteria. Investigation extended to 30 unrelated ARVC patients, performed by denaturing high-performance liquid chromatography (DHPLC), led to the identification of an additional mutation (c.1723C>T) in the 3' UTR of one proband. Neither nucleotide change was found in 300 control subjects. In vitro expression assays with constructs containing the mutations showed that mutated UTRs were twofold more active than wild-types. CONCLUSION: We identified TGFbeta3 as the disease gene involved in ARVD1. The identification of a novel ARVC gene will increase the power of the genetic screening for early diagnosis of asymptomatic carriers among relatives of ARVC patients.

3' Untranslated Regions↗
PubMed2005

Arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy is recognized as an important cause of death in young patients, particularly athletes. In the past 5 years, cardiac MRI techniques have evolved rapidly in an attempt to improve the noninvasive diagnosis of this disorder. Steady-state free precession sequences and more rapid fat saturation techniques have permitted a comprehensive and well-tolerated examination. The first formal testing of diagnostic accuracy among a broad range of readers has recently been completed. Despite these advances, limited spatial resolution and interobserver variability have prevented successful implementation of these methods. Future approaches may include high-field imaging at 3 Tesla, and viability imaging to improve diagnostic accuracy.

Arrhythmias, Cardiac↗
PubMed2005

Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RyR2 gene mutation: evidence of specific morphological substrates.

We report on a family with a history of sudden death and effort-induced polymorphic ventricular arrhythmias. The index case was a 17-year-old boy who died suddenly and at postmortem had evidence of fibrofatty replacement in the right ventricular free wall, consistent with arrhythmogenic right ventricular cardiomyopathy, as well as calcium phosphate deposits within the myocytes. A molecular genetics investigation carried out in the paraffin-embedded myocardium of the subject and in blood samples of family members disclosed a missense mutation in exon 3 (230C-->T; A77V) of the cardiac ryanodine receptor type 2 gene. The carriers showed effort-induced polymorphic ventricular tachycardia in the setting of normal resting electrocardiogram and trivial echocardiographic abnormalities, consistent with catecholaminergic polymorphic ventricular tachycardia. The observation of both arrhythmogenic right ventricular cardiomyopathy type 2 and catecholaminergic polymorphic ventricular tachycardia in the same family suggests that the two entities might correspond to different degrees of phenotypic expression of the same disease. This experience underscores the importance of a precise autopsy diagnosis in the case of sudden cardiac death, including molecular genetics, and the mission of pathologists to guide further clinical investigation of family members.

Adolescent↗
PubMed2005

Is it time to include ion channel diseases among cardiomyopathies?

Heart muscle diseases are traditionally classified according to their peculiar pathophysiologic features such as "dilated," "hypertrophic," "restrictive," and "arrhythmogenic right ventricular" cardiomyopathy. The extraordinary advances accomplished in the last two decades in molecular genetics have allowed the identification of the genetic background of most of these conditions. According to the 1995 World Health Organization definition of cardiomyopathies as "diseases of the myocardium associated with cardiac dysfunction," they should include not only forms with hemodynamic dysfunction, but also conduction and rhythm disturbances. Arrhythmias are per se a sign of cardiac dysfunction and may reflect an underlying myocardial electrical disease with or without structural abnormalities as features. Nonstructural arrhythmogenic heart diseases include long and short QT syndromes, Brugada syndrome, Lènegre disease, and catecholaminergic polymorphic ventricular tachycardia. These conditions are defined as "channelopathies" because they are the consequence of cardiac ion channel gene mutations. Long and short QT syndromes are mostly caused by either sodium or potassium ion channel gene mutations; Brugada syndrome and Lènegre disease are both related to a defective sodium channel gene; and polymorphic ventricular tachycardia is the result of an abnormal ryanodine receptor regulating calcium release from the sarcoplasmic reticulum. These nonstructural inherited arrhythmic conditions should be regarded as cardiomyopathies because the myocyte is abnormal, although the heart is apparently intact. It is time for a new classification of cardiomyopathies taking into account the underlying gene mutations and the cellular level of expression of encoded proteins, thus distinguishing cytoskeleton (cytoskeletalopathies), desmosomal (desmosomalopathies), sarcomeric (sarcomyopathies), and ion channel (channelopathies) cardiomyopathies.

Arrhythmias, Cardiac↗
PubMed2005

Surgically treated primary cardiac tumors in early infancy and childhood.

OBJECTIVE: Primary heart tumors in childhood are rare and mostly benign. Surgical treatment is advocated when symptoms or hemodynamic impairment is present. MATERIALS AND METHODS: Between 1986 and 2003, 8 children (3 males and 5 females, age ranging 5 days to 6.7 years, median 78 days) with a clinical diagnosis of cardiac mass were treated with surgery. Diagnosis was made by prenatal echocardiography in 3 patients and by 2-dimensional Doppler echocardiography in 5 patients. RESULTS: Complete surgical excision of the cardiac mass was feasible in all but 1 patient who underwent orthotopic heart transplantation. Surgical pathology examination revealed myxoma in 2 patients, fibroma in 2 patients, rhabdomyoma in 2 patients (multiple in 1), hamartoma in 1 patient, and teratoma in 1 patient. One patient died of cerebral malignancy 38 months after cardiac transplantation. At a mean follow-up of 69.2 months (range 3-190 months), all the remaining patients are asymptomatic, with good ventricular function on 2-dimensional echocardiography and no signs of residual or recurrent tumor. CONCLUSION: Surgical excision of obstructive cardiac tumors in childhood is safely feasible. Heart transplantation may represent the only therapeutic option when the tumor extensively invades the ventricular walls. Although 2-dimensional echocardiography remains a reliable diagnostic tool, a definite diagnosis of tumor histotype requires a thorough histopathologic characterization.

Age Factors↗
PubMed2004

An echocardiographic survey of primary school children for bicuspid aortic valve.

Primary school students (817 apparently healthy 10-year olds) were screened by transthoracic 2-dimensional echocardiography to assess for the prevalence of bicuspid aortic valve. Bicuspid aortic valve was found in 0.5% of cases, with a higher prevalence in males than females (0.75% vs 0.24%), and was significantly associated with aortic root enlargement compared with children who had tricuspid aortic valves.

Aortic Valve↗
PubMed2004

Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model of human disease.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. METHODS AND RESULTS: ARVC was diagnosed in 23 boxer dogs (12 male; 9.1+/-2.3 years old). Clinical events alone or in combination included sudden death (n=9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (n=19; 83%), syncope (n=12, 52%), and heart failure (n=3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (n=15, 65%) or fibrofatty (n=8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (n=8) and the left ventricle (LV) (n=11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4+/-18.8% versus 13.8+/-3.4%, respectively) (P<0.001); residual myocardium was correspondingly reduced (56.6+/-19.2% versus 84.8+/-3.8% in controls) (P<0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (n=14, 61%) and LV (n=16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. CONCLUSIONS: We describe a novel, spontaneous, and genetically transmitted animal model of ARVC associated with sudden death in the boxer dog, closely resembling the human disease. This model may aid in understanding the pathogenic mechanisms of ARVC.

Animals↗
PubMed2004

Electrocardiographic changes associated with training and discontinuation of training in an athlete with hypertrophic cardiomyopathy.

The 12-lead electrocardiogram of a 17-year-old African professional soccer player had signs of left ventricular (LV) hypertrophy and deeply inverted T waves in the inferior and precordial leads. Two-dimensional echocardiography showed mild LV hypertrophy with normal cavity size consistent with nonobstructive hypertrophic cardiomyopathy. After 5 months of complete discontinuation of training, the electrocardiogram normalized; however, the echocardiogram was unchanged. Subsequently, and contrary to our advice, the athlete resumed training and professional soccer. One year later the electrocardiogram again showed a similar and markedly abnormal pattern without cardiac dimensional changes.

Adolescent↗
PubMed2004

Cardiomyopathies: is it time for a molecular classification?

Primary myocardial diseases have always attracted the interest of the scientific community because of their obscure aetiopathogenesis. For years there was a confusion and controversy over their definition and classification. The 1995 WHO classification led to major advancements such as the introduction of a unified terminology, the official recognition of novel entities (arrhythmogenic right ventricular and idiopathic restrictive cardiomyopathies) and the definitive clarification that inflammatory heart disease has to be regarded as a cardiomyopathy. However, according to the new definition of cardiomyopathies as diseases of the myocardium associated with cardiac dysfunction, they should include not only forms with depressed contractility and impaired diastolic function, but also conduction and rhythm disturbances and enhanced arrhythmogenicity. Moreover, the recent development of molecular genetics, with the discovery of a genetic background in several forms previously defined of unknown origin, raises the need of a debate on a possible classification based on genomics.

Cardiomyopathies↗
PubMed2004

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.

Adult↗