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E. Disabella, M. Diegoli, R. Borroni,
M. Grasso,
C. Giorgianni,
M.Tagliani,
A. Pilotto,
M. Concardi,
I. Puccio,
A. Cerica,
V. Brazzelli,
E. Arbustini
XV CONGRESSO SOCIETA' ITALIANA GENETICA UMANA, Sorrento; 11/2012
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E. Disabella, M. Diegoli,
R. Borroni,
M. Grasso,
C. Giorgianni,
M.Tagliani,
A. Pilotto,
M. Concardi,
I. Puccio,
A. Cerica,
V. Brazzelli,
E. Arbustini
XV Congresso società italiana genetica umana, sorrento; 11/2012
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XV Congresso società italiana genetica umana., Sorrento; 11/2012
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E. Disabella, M. Diegoli, R. Borroni,
M. Grasso,
C. Giorgianni,
M. Tagliani,
A. Pilotto,
A. Scarabotto,
M. Concardi,
I. Puccio,
E. Arbustini
XV CONGRESSO SOCIETA' ITALIANA GENETICA UMANA., Sorrento; 11/2012
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M. Diegoli,
M. Grasso,
E. Disabella,
M. Concardi,
I. Puccio,
A. Serio,
V. Favalli,
F.I.Gambarin,
M. Tagliani,
A. Pilotto,
C. Giorgianni
XIV Congresso società italiana genetica umanan, Milano; 11/2011
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M. Diegoli,
M. Grasso,
E. Disabella,
M. Concardi,
I. Puccio,
A. Serio,
V. Favalli,
F.I.Gambarin,
M. Tagliani,
A. Pilotto,
C. Giorgianni,
E.Arbustini
XIV CONGRESSO SOCIETA' ITALIANA GENETICA UMANA., milano; 11/2011
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ABSTRACT: Glomangiomatosi familiare: mutazione del gene GLMN in una famiglia italiana con malformazioni glomovenose cutanee
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Eloisa Arbustini,
N Marziliano,
E Porcu,
M Pasotti,
M Grasso,
M Tagliani,
E Disabella, M Diegoli,
A Pilotto,
S Ghio,
C Campana,
A D'Armini,
M Viganò
Human Genetics 03/2008; 123(1):112-3. · 5.07 Impact Factor
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Human Genetics 03/2007; 120(6):910. · 5.07 Impact Factor
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Neurology 12/2006; 67(9):1715-7. · 8.31 Impact Factor
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Human Genetics 08/2006; 119(6):682. · 5.07 Impact Factor
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Human Genetics 01/2006; 118(3-4):536. · 5.07 Impact Factor
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Human Genetics 08/2005; 117(2-3):295. · 5.07 Impact Factor
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Human Genetics 08/2005; 117(2-3):297. · 5.07 Impact Factor
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Human Genetics 08/2005; 117(2-3):297. · 5.07 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Mitochondrial DNA (mtDNA) mutations have been causally linked with cardiomyopathies, both dilated (DCM) and hypertrophic. We identified the T12297C mutation in the mtDNA-tRNA(Leu(CUN)) of a 36-year-old male patient diagnosed with DCM. The mutation was heteroplasmic, with high amount (88%) of mutant DNA in the myocardium, and was absent in normal (n = 120) and disease (n = 150) controls. It affects a highly conserved nucleotide (adjacent to the anticodon triplet) that allows the phospho-ribose backbone to turn and form the loop. The potential pathological role of T12297C mutation is further supported by its recent identification in another unrelated Italian family with DCM associated with endocardial fibroelastosis. In the variable loop of the same tRNA, our patient also carried the A12308G transition that is debated as pathological mutation or neutral polymorphism in progressive external ophthalmoplegia: the two defects could exert a synergistic effect on the tRNA structure and function. The endomyocardial biopsy study showed abnormal ring-like mitochondria and occasional cytochrome c oxydase negative myocytes. Overall, the heteroplasmy, the highly conserved position of the mutated nucleotide, the absence of the mutation in large series of diseased and normal controls, and the cardiac mitochondrial changes support a causative link of the mutation with the disease.
European Journal of HumanGenetics 05/2001; 9(4):311-5. · 4.40 Impact Factor
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A Gavazzi,
A Repetto,
L Scelsi,
C Inserra,
M L Laudisa,
C Campana,
C Specchia,
B Dal Bello, M Diegoli,
L Tavazzi,
E Arbustini
[show abstract]
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ABSTRACT: To assess the prevalence of familial non-X-linked dilated cardiomyopathy, to diagnose early asymptomatic cases evaluate inheritance and characterize clinical phenotypes.
We screened 472 relatives of 104 consecutive patients diagnosed with dilated cardiomyopathy; males with X-linked dilated cardiomyopathy were excluded based on systematic immunohistochemical and molecular analysis. Relatives underwent clinical examination, electrocardiography, echocardiography and serum creatine-phosphokinase determination. Twenty-six index patients (25%) had familial disease: four youths (< or = 20 years) had rapidly progressive outcome and underwent emergency transplantation. In a sib-pair, the onset was with atrioventricular block. Inheritance was autosomal dominant in 15, undetermined in seven (four sib-pairs); mitochondrial DNA pathological mutations were found in four. The screening identified 23 newly diagnosed relatives in the familial group. Transplantation (P = 0.04) and atrial fibrillation (P = 0.04) were more frequent, and left bundle branch block (P = 0.04) less frequent in index patients with familial than in those with non-familial disease. Several non-affected relatives had instrumental abnormalities potentially useful as pre-clinical markers: their prevalence was similar in both groups.
The prevalence of familial, non X-linked dilated cardiomyopathy was 25%. The immediate benefits of screening family members of index patients was early diagnosis in unaware symptomless affected relatives.
European Heart Journal 01/2001; 22(1):73-81. · 10.48 Impact Factor
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E Arbustini, M Diegoli,
P Morbini,
B Dal Bello,
N Banchieri,
A Pilotto,
F Magani,
M Grasso,
J Narula,
A Gavazzi,
M Viganò,
L Tavazzi
[show abstract]
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ABSTRACT: To assess the prevalence of dystrophin defects in dilated cardiomyopathy (DCM) in male patients and to formulate investigation strategies for their identification.
Dystrophin defects presenting with predominant or exclusive cardiac involvement may be clinically indistinguishable from "idiopathic" DCM. Diagnosis may be missed, unless specifically investigated.
Clinical and biochemical evaluation, right ventricular endomyocardial biopsy (EMB), light and electron microscopic and immunohistochemical studies of biopsy samples, six multiplex and two single polymerase chain reactions for 38 exons and automated sequencing of exon 9 and muscle promoter-exon 1 were undertaken in 201 consecutive male patients presenting with DCM, with (n = 14) and without (n = 187) increased serum creatine phosphokinase (sCPK).
Dystrophin defects were identified in 13 of the 201 patients (6.5%, age 16-50). Family history was positive in four patients. Serum CPK levels were increased in 11 of 13 patients. Light microscopy examination of EMB was uninformative; ultrastructural study showed multiple membrane defects. Dystrophin immunostain was abnormal. Eight patients, all older than 20, had deletions affecting midrod domain, normal or mildly increased CPK and better outcome than the five remaining cases all younger than 20, with more than five-fold increase of sCPK. Two of these latter had proximal and rod-domain deletions. Sisters of two patients were diagnosed as noncarriers with microsatellite analysis.
Although the overall prevalence of dystrophin defects in our consecutive DCM male series is low (6.5%), immunohistochemical and molecular studies are essential to identify protein and gene defects; screening studies are justified to define prevalence, clinical profile and genotype-phenotype correlation.
Journal of the American College of Cardiology 07/2000; 35(7):1760-8. · 14.16 Impact Factor
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E Arbustini,
E Porcu,
O Bellini,
M Grasso,
A Pilotto,
B Dal Bello,
P Morbini, M Diegoli,
A Gavazzi,
G Specchia,
L Tavazzi
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ABSTRACT: Enteroviral RNA detection in myocarditis and dilated cardiomyopathy is rare. Enteroviral particles and RNA have recently been identified in patient's skeletal muscle, suggesting that skeletal more than heart muscle hosts the virus in chronic infection. Enteroviral RNA and virus-like particles were found in the myocardium and in the skeletal muscle of two patients with fatal myocarditis: a 39 year old man who died five days after the onset of febrile flu; and a 49 year old woman, assisted for 50 days with a left ventricular assist device, who then died from cerebral haemorrhage. Automated sequencing, alignment, and sequence comparison confirmed the enteroviral origin of polymerase chain reaction products and excluded contamination. These findings agree with prior observations of enteroviral localisation in the skeletal muscle of patients with dilated cardiomyopathy, and further support the hypothesis that skeletal rather than heart muscle may host the virus and serve as a reservoir in cardiomyopathies related to chronic infection.Keywords: enterovirus; myocarditis; viral particles; skeletal muscle
Heart (British Cardiac Society) 01/2000; 83(1):86-90. · 4.22 Impact Factor
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E Arbustini, M Diegoli,
R Fasani,
M Grasso,
P Morbini,
N Banchieri,
O Bellini,
B Dal Bello,
A Pilotto,
G Magrini,
C Campana,
P Fortina,
A Gavazzi,
J Narula,
M Viganò
[show abstract]
[hide abstract]
ABSTRACT: Mitochondrial (mt)DNA defects, both deletions and tRNA point mutations, have been associated with cardiomyopathies. The aim of the study was to determine the prevalence of pathological mtDNA mutations and to assess associated defects of mitochondrial enzyme activity in dilated cardiomyopathy (DCM) patients with ultrastructural abnormalities of cardiac mitochondria. In a large cohort of 601 DCM patients we performed conventional light and electron microscopy on endomyocardial biopsy samples. Cases with giant organelles, angulated, tubular, and concentric cristae, and crystalloid or osmiophilic inclusion bodies were selected for mtDNA analysis. Mutation screening techniques, automated DNA sequencing, restriction enzyme digestion, and densitometric assays were performed to identify mtDNA mutations, assess heteroplasmy, and quantify the amount of mutant in myocardial and blood DNA. Of 601 patients (16 to 63 years; mean, 43.5 +/- 12.7 years), 85 had ultrastructural evidence of giant organelles, with abnormal cristae and inclusion bodies; 19 of 85 (22.35%) had heteroplasmic mtDNA mutations (9 tRNA, 5 rRNA, and 4 missense, one in two patients) that were not found in 111 normal controls and in 32 DCM patients without the above ultrastructural mitochondrial abnormalities. In all cases, the amount of mutant was higher in heart than in blood. In hearts of patients that later underwent transplantation, cytochrome c oxidase (Cox) activity was significantly lower in cases with mutations than in those without or controls (P = 0.0008). NADH dehydrogenase activity was only slightly reduced in cases with mutations (P = 0.0388), whereas succinic dehydrogenase activity did not significantly differ between DCM patients with mtDNA mutations and those without or controls. The present study represents the first attempt to detect a morphological, easily identifiable marker to guide mtDNA mutation screening. Pathological mtDNA mutations are associated with ultrastructurally abnormal mitochondria, and reduced Cox activity in a small subgroup of non-otherwise-defined, idiopathic DCMs, in which mtDNA defects may constitute the basis for, or contribute to, the development of congestive heart failure.
American Journal Of Pathology 12/1998; 153(5):1501-10. · 4.89 Impact Factor
