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Bruno Marino

Publications and source records attributed to Bruno Marino.

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

NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome.

Neurofibromatosis type 1 (NF1) demonstrates phenotypic overlap with Noonan syndrome (NS) in some patients, which results in the so-called neurofibromatosis-Noonan syndrome (NFNS). From a genetic point of view, NFNS is a poorly understood condition, and controversy remains as to whether it represents a variable manifestation of either NF1 or NS or is a distinct clinical entity. To answer this question, we screened a cohort with clinically well-characterized NFNS for mutations in the entire coding sequence of the NF1 and PTPN11 genes. Heterozygous NF1 defects were identified in 16 of the 17 unrelated subjects included in the study, which provides evidence that mutations in NF1 represent the major molecular event underlying this condition. Lesions included nonsense mutations, out-of-frame deletions, missense changes, small inframe deletions, and one large multiexon deletion. Remarkably, a high prevalence of inframe defects affecting exons 24 and 25, which encode a portion of the GAP-related domain of the protein, was observed. On the other hand, no defect in PTPN11 was observed, and no lesion affecting exons 11-27 of the NF1 gene was identified in 100 PTPN11 mutation-negative subjects with NS, which provides further evidence that NFNS and NS are genetically distinct disorders. These results support the view that NFNS represents a variant of NF1 and is caused by mutations of the NF1 gene, some of which have been demonstrated to cause classic NF1 in other individuals.

Child↗
PubMed2005

Familial recurrence of heart defects in subjects with congenitally corrected transposition of the great arteries.

Familial recurrence of congenitally corrected transposition of the great arteries (CCTGA) is considered uncommon. Most of the previous familial studies involved a small number of patients and referred to all situs and looping anomalies including single ventricle, heterotaxia, and other cardiac defects different from CCTGA. We performed a large, consecutive clinical case series study in order to detect the recurrence of congenital heart defects in families of children with the classic form of CCTGA. From January 1997 through December 2004, 102 consecutive patients with CCTGA were evaluated in four institutions. There were 59 male (57.8%) and 43 female (42.2%). Mean age was 8.6 +/- 7.8 years. Eighty-eight patients (86.3%) had situs solitus of the atria, 14 (13.7%) situs inversus. The cardiac and extracardiac anomalies among relatives and the patterns of familial recurrence were investigated. Relatives with congenital heart defects were found in 16/102 families (15.7%). Transposition of the great arteries (TGA) was the most common recurrent defect (6/102 families). Consanguinity was identified in the parents of three probands. Six probands had an unaffected twin-sib. Recurrence risks for congenital heart defects were calculated at 5.2% (6/116) for siblings. In conclusion, CCTGA is not always sporadic in families. The pattern of inheritance, the presence of consanguinity among parents and the recurrence of situs inversus could suggest, in some families, an autosomal recessive mechanism with similarities with that occurring in some pedigrees with heterotaxia. The recurrence of TGA and CCTGA in the same family suggests a pathogenetic link between these two anatomically different malformations.

Family Health↗
PubMed2005

Familial recurrence of nonsyndromic congenital heart defects in first degree relatives of patients with deletion 22q11.2.

The majority of nonsyndromic congenital heart defects (CHDs) are considered to follow a multifactorial model of inheritance. Multiple family members affected by CHD can occasionally be detected, and the involvement of several genetic loci interacting with environmental factors is suspected to be implicated. The DiGeorge/velo-cardio-facial syndrome related to microdeletion 22q11.2 (del22) is a genetic condition associated with CHD in most of the cases. We report here on five pedigrees of patients with del22, showing occurrence of nonsyndromic CHD in a first-degree relative of the proband case. Familial aggregation of syndromic and nonsyndromic CHD as observed in our series is to be considered as an unusual pattern of recurrence. The interaction between several different genes and environmental factors, a familial susceptibility predisposing to a specific cardiac malformation, or chance association can all be hypothesized searching an explanation for these particular observations.

Chromosome Deletion↗
PubMed2005

ZFPM2/FOG2 and HEY2 genes analysis in nonsyndromic tricuspid atresia.

Tricuspid atresia (TriAt), the third most common cyanotic congenital heart defect (CHD), consists of complete lack of tricuspid valve formation, with no connection between the right atrium and the right ventricle. To date, the genetic mechanism responsible of TriAt is still obscure. However, animal models have suggested a role of cardiogenic Zfpm2/Fog2 and Hey2 genes in the pathogenesis of TriAt. Therefore, we screened 40 individuals affected by nonsyndromic TriAt for ZFPM2/FOG2 and HEY2 gene mutations. No pathogenetic mutation has been identified, thus failing to demonstrate a major role of ZFPM2/FOG2 and HEY2 genes in the pathogenesis of human TriAt.

Adolescent↗
PubMed2004

Familial aggregation of genetically heterogeneous hypertrophic cardiomyopathy: a boy with LEOPARD syndrome due to PTPN11 mutation and his nonsyndromic father lacking PTPN11 mutations.

BACKGROUND: Nonsyndromic hypertrophic cardiomyopathy (HCM) is a primary cardiac disease transmitted as an autosomal dominant trait. Multiple chromosomal loci have been found to be involved in the etiology of this defect. LEOPARD syndrome is a genetic condition characteristically associated with HCM. Additional features of the syndrome include multiple lentigines, facial anomalies, sensorineural deafness, and growth retardation. Mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at chromosome 12q24, have been identified in patients with LEOPARD syndrome. CASES: We report here on a patient with HCM presenting with classic clinical features of LEOPARD syndrome, whose father also has HCM, but lacks phenotypic anomalies of the syndrome. Molecular analysis searching for PTPN11 mutations was performed in this family. A missense mutation (836A-->G; Tyr279Cys) in exon 7 of PTPN11 gene was identified in the patient with LEOPARD syndrome, whereas no mutation in PTPN11 gene was detected in the father or in additional family members. CONCLUSIONS: Aggregation of syndromic and nonsyndromic HCM in the same family is an unusual pattern of recurrence. Although genetic heterogeneity of LEOPARD and nonsyndromic HCM is not disputed, the existence of peculiar interactions linking genes causing nonsyndromic HCM and HCM in LEOPARD syndrome can be hypothesized. Different genes can work together, and a more severe cardiac phenotype can be due to additive effects. The involvement of familial susceptibility to specific cardiac malformations based on the presence of common predisposing factors can also be considered. Further molecular studies may shed light on these observations.

Adult↗
PubMed2004

Better surgical prognosis for patients with complete atrioventricular septal defect and Down's syndrome.

BACKGROUND: Several studies have shown that Down's syndrome is not a risk factor for biventricular repair of complete atrioventricular septal defects. However, few data are available about the comprehensive outcome of all the cardiac surgical procedures in patients with trisomy 21, including palliative surgery. METHODS: This is a retrospective study of 206 consecutive patients who underwent cardiac surgery from January 1992 to January 2002. Data about mortality and morbidity were analyzed and the impact of Down's syndrome was evaluated. RESULTS: Overall mortality was 7.7%. Actuarial survival was 94% among patients with Down's syndrome versus 86% of the group with normal karyotype (p = 0.12). The presence of unbalanced ventricles was the only independent risk factor affecting survival at multivariate analysis (p < 0.0001). The need for a Norwood type surgery was more frequent among non-Down patients (12.0% vs 1.5%, p = 0.02) as was the prevalence of pulmonary artery banding operations (22.9% vs 9.3%, p = 0.04). Cumulative mortality after palliation was higher in non-Down patients (44% vs 2.9%, p = 0.0001). Freedom from reoperation was lower in the group with normal chromosomes in respect to patients with Down's syndrome (81.4% vs 94.6%, p = 0.04), due to the higher prevalence of anomalies of the mitral valve (4.9% vs 1.8%, p = 0.03) or left ventricular outflow tract (7.3% vs 0%, p = 0.01). CONCLUSIONS: Down patients showed a decreased risk for biventricular repair and lower mortality and morbidity in cases of complex cardiac malformations requiring complex palliative operations.

Abnormalities, Multiple↗
PubMed2004

Conotruncal heart defects: impact of genetic syndromes on immediate operative mortality.

BACKGROUND: The surgical outcome of conotruncal heart defects in patients with genetic syndromes has been poorly studied. The aim of this prospective 5-year multicenter study was to elucidate the post-surgical death rate of children with conotruncal heart defects in relation to the presence of associated genetic syndromes. METHODS: Two institutions enrolled 350 consecutive inpatients with conotruncal heart defects, aged between 1 day and 60 months, who were submitted to surgery; all patients were evaluated by a clinical geneticist and had a standard metaphase chromosome analysis and a fluorescent in situ hybridization study searching for deletion of chromosome 22q11 (del22q11). RESULTS: No genetic syndrome was diagnosed in 289 patients; among the other 61 patients, 27 had DiGeorge velocardiofacial syndrome (del22q11), 16 patients had Down syndrome, and 18 presented with other genetic syndromes. The overall post-surgical death rate was higher in syndromic patients (18%) than in non-syndromic ones (10.7%) with a relative risk of 1.9 (p = 0.06). However, children with del22q11 showed a higher risk for surgical mortality (25.9 vs 10.7%; relative risk 2.4, p = 0.03). Del22q11 was identified as a risk factor for immediate surgical mortality in patients with pulmonary atresia and ventricular septal defect and in patients with interrupted aortic arch. CONCLUSIONS: Down syndrome is not a risk factor for surgery in children with conotruncal heart defects. The presence of a del22q11 may influence the surgical results in children with pulmonary atresia and ventricular septal defect and in those with interrupted aortic arch. Patients with genetic syndromes other than del22q11 and Down syndrome have a higher surgical mortality compared to that observed in non-syndromic patients. These data may be useful for preoperative counseling and for the elaboration of specific protocols of perioperative treatment.

Child, Preschool↗