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Bruno Marino

Publications and source records attributed to Bruno Marino.

50 records · Page 3Linked to original sources
PubMed2003

Specific congenital heart defects in RSH/Smith-Lemli-Opitz syndrome: postulated involvement of the sonic hedgehog pathway in syndromes with postaxial polydactyly or heterotaxia.

BACKGROUND: RSH/Smith-Lemli-Opitz syndrome is an autosomal recessive syndrome due to an inborn error of cholesterol metabolism and is characterized by developmental delay, facial anomalies, hypospadias, congenital heart defect (CHD), postaxial polydactyly, and 2-3 toe syndactyly. CHD is found in half of the propositi, and a specific association with atrioventricular canal defect (AVCD) and anomalous pulmonary venous return has been demonstrated. METHODS: We report on an additional patient with RSH/SLOS presenting with complete AVCD and anomalous pulmonary venous return, and discuss the possible relationship of the Sonic Hedgehog (SHH) pathway as causative factor of these CHDs and those in heterotaxia patients with postaxial polydactyly syndromes. RESULTS: Anatomic similarities between heterotaxia and CHDs of several syndromes with postaxial polydactyly have been noted previously, considering the frequent association of AVCD with common atrium in these conditions. It is known that both CHDs of heterotaxia and postaxial polydactyly can be related to abnormalities of the SHH pathway. Cholesterol has a critical role in the formation of normally active hedgehog proteins. It could be hypothesized that specific types of CHDs in RSH/SLOS can be caused by modifications of the SHH protein related to the defect of cholesterol biosynthesis. CONCLUSIONS: The specific association of AVCD and anomalous pulmonary venous return in patients with RSH/SLOS and the finding of AVCD +/- common atrium in several syndromes with polydactyly leads to the hypothesis that heterotaxia due to SHH anomalies could be involved in a large spectrum of conditions. Perturbations in different components of the SHH pathway could lead to several developmental errors presenting with partially overlapping clinical manifestations.

Consanguinity↗
PubMed2003

Mutations of ZFPM2/FOG2 gene in sporadic cases of tetralogy of Fallot.

Two out of 47 patients with sporadic tetralogy of Fallot (TOF), the most common cyanotic conotruncal heart defect (CTD), showed heterozygous missense mutations of the ZFPM2/FOG2 gene. Knockout mice carrying mutations in the ZFPM2/FOG2 gene have similarly been found to exhibit TOF. While both mutant ZFPM2/FOG2 proteins, E30G (c.88A>G) and S657G (c.1968A>G), retain the ability to bind the partner protein GATA4 and repress GATA4 mediated gene activation, the S657G, but not the E30G, mutation is subtly impaired in this function. ZFPM2/FOG2 gene mutations may contribute to some sporadic cases of TOF.

Adolescent↗
PubMed2003

DiGeorge subtypes of nonsyndromic conotruncal defects: evidence against a major role of TBX1 gene.

The role of the 22q11 region genes, and among them TBX1, in nonsyndromic conotruncal defects (CTDs) is still unclear. Mice hemizygous at the Tbx1 locus show a remarkable incidence of heart outflow tract anomalies, of the same type commonly found in DiGeorge/Velo-cardio-facial syndrome (DGS/VCFS). Mutation analysis of the TBX1 gene in isolated, nonsyndromic CTDs has not demonstrated any functional pathogenetic variation so far. We screened the TBX1 gene in 41 patients affected by nonsyndromic CTDs of the DGS/VCFS subtype, principally "atypical" tetralogy of Fallot. Besides a few polymorphisms, we did not find any pathogenetic variation. These results do not support a major role of the TBX1 gene as responsible for human nonsyndromic CTDs.

Adolescent↗
PubMed2002

Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene.

Multiple-lentigines (ML)/LEOPARD (multiple lentigines, electrocardiographic-conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) syndrome is an autosomal dominant condition--characterized by lentigines and café au lait spots, facial anomalies, cardiac defects--that shares several clinical features with Noonan syndrome (NS). We screened nine patients with ML/LEOPARD syndrome (including a mother-daughter pair) and two children with NS who had multiple café au lait spots, for mutations in the NS gene, PTPN11, and found, in 10 of 11 patients, one of two new missense mutations, in exon 7 or exon 12. Both mutations affect the PTPN11 phosphotyrosine phosphatase domain, which is involved in <30% of the NS PTPN11 mutations. The study demonstrates that ML/LEOPARD syndrome and NS are allelic disorders. The detected mutations suggest that distinct molecular and pathogenetic mechanisms cause the peculiar cutaneous manifestations of the ML/LEOPARD-syndrome subtype of NS.

Adolescent↗
PubMed2002

Pulmonary atresia with intact ventricular septum and systemic-pulmonary collateral arteries.

Pulmonary atresia with intact ventricular septum and major systemic-pulmonary collateral arteries is a very rare congenital heart lesion with dismal natural history. Herein we report on a case of pulmonary atresia with intact ventricular septum with hypoplastic right ventricle, very small confluent pulmonary arteries, absent arterial duct, and pulmonary blood flow exclusively provided by bronchial-type systemic-pulmonary collateral arteries that was successfully treated at our institution.

Anastomosis, Surgical↗
PubMed2002

[Transposition of great arteries. Understanding its pathogenesis].

Transposition of the great arteries (TGA) is a frequent and severe cardiac defect. In patients with this malformation, diagnostic and surgical results and the long-term prognosis significantly improved in the last years. From the embryological point of view there are two main theories: 1) the anomalous infundibular rotation, and 2) the anomaly of the aortico-pulmonary septum. Both of them still present important limits. Moreover, TGA is difficult to reproduce by animal experiments, but interesting data, using retinoid acid in pregnant rats, are nowadays available, as well as there are interesting data from the epidemiologic studies on human teratologic agents. TGA is rarely associated with genetic syndromes and with additional extracardiac anomalies. A few cases are in relation with DiGeorge syndrome with deletion of chromosome 22q11. On the contrary TGA is significantly prevalent, in association with other cardiac and extracardiac anomalies, in children with lateralization defects, heterotaxy and asplenia syndrome (right isomerism). However in patients with heterotaxy and polysplenia syndrome (left isomerism) TGA is significantly more rare. In mice with mutation of Smad2 and NODAL, two genes involved in the lateralization process, some cases of TGA, with or without right isomerism of the lungs, were reported. Moreover, in families with heterotaxy some cases with congenitally corrected TGA were reported and a new gene associated with heterotaxy, CRYPTIC, can present mutations in patients with "isolated" TGA. A recent study on familiar recurrence of TGA shows in the same family some cases of TGA and of corrected TGA so that a monogenic inheritance (autosomic dominant or recessive) with variable phenotypic expression can be suggested. The normal righthand spiralization of the heart is genetically determined in cases of situs solitus and d-loop of the ventricles. This pattern is not present in cases of TGA presenting a parallel position of the great arteries. On the basis of these observations and according to new epidemiologic and genetic data some cases of TGA should be classified in the group of the anomalies of lateralization and ventricular loop. The mystery is still present but perhaps some gleams of light are appearing.

Animals↗
PubMed1981

Morphology of aortic arch obstruction with patent ductus arteriosus.

Thirty-one hearts with aortic arch obstruction and patent ductus arteriosus were examined with special reference to associated cardiac anomalies. Six presented with complete interruption of the aortic arch, four with atretic isthmus, twelve with coarctation, and three with tubular hypoplasia. Associated cardiac anomalies were divided into two main groups: (1) septal defect with left-to-right shunt, and (2) left ventricular inflow and/or outflow obstruction. A high incidence (9/19=47.4%) of ventriculo-infundibular malalignment type of ventricular septal defect with subaortic stenosis was observed. Associated cardiac lesions that reduce blood flow in the aortic arch during fetal life may be responsible for poor development of this structure.

Journal Article↗
PubMedDate not supplied

A multiple retinoic acid antagonist induces conotruncal anomalies, including transposition of the great arteries, in mice.

BACKGROUND: The morphogenetic mechanisms that are responsible for the transposition of the great arteries are still largely unknown, mainly because this malformation is very difficult to experimentally reproduce. The aim of the present study was to test the effect of BMS-189453, a retinoic acid antagonist, on murine heart morphogenesis. METHODS: We administered this drug at 5 mg/kg body weight (twice, at a 12-h interval) to pregnant mice on 6.25/6.75 days postcoitum (dpc) (Group A), 6.75/7.25 dpc (Group B), 7.25/7.75 dpc (Group C), 7.75/8.25 dpc (Group D), or 8.25/8.75 dpc (Group E). At birth, the anatomical features of fetuses were evaluated by stereomicroscopic examination. RESULTS: In Group A (18 fetuses), cardiovascular anatomy was normal in 10 (56%) cases, and 8 (44%) fetuses presented with transposition of the great arteries. In Group B, no fetuses were obtained. In Group C (78 fetuses), cardiovascular anatomy was normal in 19 (24%) cases, while 59 (76%) mice presented with various types of cardiac defects, including 48 transpositions of the great arteries (61%). In Group D (80 fetuses), cardiac defects were seen in 22 (27%) mice: 14 of these (17%) were transpositions of the great arteries. In Group E (72 fetuses), cardiovascular anatomy was normal in all cases. Of 248 fetuses analyzed, 87% presented with thymic aplasia or hypoplasia, and 20% presented with meroanencephalia and/or rachischisis. CONCLUSIONS: Transposition of the great arteries can be consistently reproduced in mice by administration of a retinoic acid competitive antagonist on 7.5 dpc.

Abnormalities, Drug-Induced↗