Carlo Cianchetti

Bio: Carlo Cianchetti is an academic researcher from University of Cagliari. The author has contributed to research in topics: Migraine & Subacute sclerosing panencephalitis. The author has an hindex of 28, co-authored 108 publications receiving 2864 citations. Previous affiliations of Carlo Cianchetti include University of Trieste.

Brief report - deletion of the dystrophin muscle-promoter region associated with x-linked dilated cardiomyopathy

Abstract: Several forms of hereditary dilated cardiomyopathy have been identified; with the exception of those resulting from mutations of mitochondrial DNA,1,2 no pathological finding can be used to differentiate the conditions, so their distinction depends on the pattern of transmission. Autosomal recessive, autosomal dominant, and matrilinear forms have been reported; several families with X-linked dilated cardiomyopathy have also been described3–5. X-linked dilated cardiomyopathy is a progressive myocardial disease presenting as congestive heart failure in teenage boys without clinical signs of skeletal myopathy5. No information is available on the pathogenetic defect involved in this disorder, although cardiomyopathy is . . .

Increased Sensitivity of the Neuronal Nicotinic Receptor α2 Subunit Causes Familial Epilepsy with Nocturnal Wandering and Ictal Fear

Abstract: Sleep has traditionally been recognized as a precipitating factor for some forms of epilepsy, although differential diagnosis between some seizure types and parasomnias may be difficult. Autosomal dominant frontal lobe epilepsy is characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements and has been associated with mutations of the α4 and β2 subunits of the neuronal nicotinic acetylcholine receptor. We performed a clinical and molecular genetic study of a large pedigree segregating sleep-related epilepsy in which seizures are associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. We identified a new genetic locus for familial sleep-related focal epilepsy on chromosome 8p12.3-8q12.3. By sequencing the positional candidate neuronal cholinergic receptor α2 subunit gene (CHRNA2), we detected a heterozygous missense mutation, I279N, in the first transmembrane domain that is crucial for receptor function. Whole-cell recordings of transiently transfected HEK293 cells expressing either the mutant or the wild-type receptor showed that the new CHRNA2 mutation markedly increases the receptor sensitivity to acetylcholine, therefore indicating that the nicotinic α2 subunit alteration is the underlying cause. CHRNA2 is the third neuronal cholinergic receptor gene to be associated with familial sleep-related epilepsies. Compared with the CHRNA4 and CHRNB2 mutations reported elsewhere, CHRNA2 mutations cause a more complex and finalized ictal behavior.

Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein zero gene

Abstract: Charcot-Marie-Tooth disease (CMT), or hereditary motor and sensory neuropathy (HMSN), is a clinically and genetically heterogeneous condition. Mutations of the myelin protein zero ( MPZ ) gene have been associated with CMT1B, Dejerine-Sottas disease, and congenital hypomyelination, which are inherited demyelinating neuropathies characterized by different clinical severity. HMSN type II (HMSN II) or CMT2, the axonal form of CMT, is genetically heterogeneous. Linkage to 1p35-p36 (CMT2A), 3q(CMT2B), and 7p (CMT2D) chromosomes has been reported in the disease; however, most HMSN II families do not link to any of the reported loci. In a large HMSN II Sardinian family, we found a missense mutation in the chromosome 1q MPZ gene. This Ser 44 Phe mutation was located in exon 2 and was present in the heterozygous state in all affected individuals. This is the first example of an HMSN II family showing an MPZ point mutation. The MPZ gene Ser 44 Phe mutation found in the HMSN II family presented in this study suggests that genetic analysis of HMSN II families should also include the MPZ gene, previously not considered to be involved in the axonal form of HMSN.

A mutation in the dystrophin gene selectively affecting dystrophin expression in the heart.

Abstract: We have previously shown in a large X-linked pedigree that a deletion removing the dystrophin muscle promoter, the first muscle exon and part of intron 1 caused a severe dilated cardiomyopathy with no associated muscle weakness. Dystrophin expression was present in the muscle of affected males and transcription studies indicated that this dystrophin originated from the brain and Purkinje cell isoforms, upregulated in this skeletal muscle. We have now studied dystrophin transcription and expression in the heart of one member of this family. In contrast to the skeletal muscle, dystrophin transcription and expression were absent in the heart, with the exception of the distal Dp71 dystrophin isoform, normally present in the heart. The 43- and 50-kD dystrophin-associated proteins were severely reduced in the heart, despite the presence of Dp71, but not in skeletal muscle. The absence of dystrophin and the down-regulation of the dystrophin-associated proteins in the heart accounted for the severe cardiomyopathy in this family. The mutation present in these males selectively affects dystrophin expression in the heart; this could be secondary to the removal of cardiac-specific regulatory sequences. This family may represent the first example of a mutation specifically affecting the cardiac expression of a gene, present physiologically in both the skeletal and cardiac muscles.

Long-Term Risperidone for Pervasive Developmental Disorder: Efficacy, Tolerability, and Discontinuation

Abstract: To investigate the safety (e.g., weight gain, liver function, extrapyramidal side effects, and seizures) and efficacy of the long-term use of risperidone in children and adolescents and to ascertain the effects of drug withdrawal in a semi-naturalistic prospective, subjects with autism or pervasive developmental disorders not otherwise specified (PDDNOS) were treated with risperidone for 6 months after which parents were given the option of continuing for a further 6 months (final assessment at 12 months). Behavioral rating included Childhood Autism Rating Scale (CARS), Child Psychiatric Rating Scale (CPRS), Clinical Global Impression (CGI), and Child-Global Assessment Scale (C-GAS). Risperidone significantly ameliorated behavioral symptoms of PDD in 10 out of 11 subjects, with the effects on core symptoms being of smaller amplitude and of slower onset. No loss of effectiveness was observed in patients who continued risperidone for 12 months, while a relapse of associated behavioral symptoms occurred in the others. Weight gain was common, although the rate of increase lessened over a period of time; after drug withdrawal, considerable weight loss was observed in the patient who had previously shown the most significant increase. After 6 months of therapy, two patients developed facial dystonia: this disappeared after reducing dosage in one case, after drug discontinuation in the other. Amenorrhea was also observed, but no changes in liver function, blood tests or EEG were reported. The data indicate that risperidone is an effective and relatively safe drug for long term treatment of behavioral disruption in autistic children and adolescents.

The Nervous System

Abstract: Experimental Neurology By Prof Paul Glees Pp xii + 532 (Oxford: Clarendon Press; London: Oxford University Press, 1961) 75s net

Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.

Abstract: Background Inherited mutations cause approximately 35 percent of cases of dilated cardiomyopathy; however, few genes associated with this disease have been identified. Previously, we located a gene defect that was responsible for autosomal dominant dilated cardiomyopathy and conduction-system disease on chromosome 1p1–q21, where nuclear-envelope proteins lamin A and lamin C are encoded by the LMNA (lamin A/C) gene. Mutations in the head or tail domain of this gene cause Emery–Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood. Methods We evaluated 11 families with autosomal dominant dilated cardiomyopathy and conduction-system disease. Sequences of the lamin A/C exons were determined in probands from each family, and variants were confirmed by restriction-enzyme digestion. The genotypes of the family members were ascertained. Results Five novel missense mutations were identified: four in the α...

International Classification of Headache Disorders

Abstract: A set of related medical disorders that lack a proper classification system and diagnostic criteria is like a society without laws. The result is incoherence at best, chaos at worst. For this reason, the International Classification of Headache Disorders (ICHD) is arguably the single most important breakthrough in headache medicine over the last 50 years. The ICHD identifies and categorizes more than a hundred different kinds of headache in a logical, hierarchal system. Even more important, it has provided explicit diagnostic criteria for all of the headache disorders listed. The ICHD quickly became universally accepted, and criticism of the classification has been minor relative to that directed at other disease classification systems. Over the 20 years following publication of the first edition of the ICHD, headache research has rapidly accelerated despite sparse allocation of resources to that effort. In summary, the ICHD has attained widespread acceptance at the international level and has substantially facilitated both clinical research and clinical care in the field of headache medicine.

Dystrophin and mutations: one gene, several proteins, multiple phenotypes

Abstract: Summary A large and complex gene on the X chromosome encodes dystrophin. Many mutations have been described in this gene, most of which affect the expression of the muscle isoform, the best-known protein product of this locus. These mutations result in the Duchenne and Becker muscular dystrophies (DMD and BMD). However, there are several other tissue specific isoforms of dystrophin, some exclusively or predominantly expressed in the brain or the retina. Mutations affecting the correct expression of these tissue-specific isoforms have been associated with the CNS involvement common in DMD. Rare mutations also account for the allelic disorder X-linked dilated cardiomyopathy, in which dystrophin expression or function is affected mostly or exclusively in the heart. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has provided insights into several regulatory mechanisms governing the gene expression profile. Here, we focus on current understanding of the genotype–phenotype relation for mutations in the dystrophin gene and their implications for gene functions.

Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice

Abstract: Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane Here we show that LAMP-2 deficiency in mice increases mortality between 20 and 40 days of age The surviving mice are fertile and have an almost normal life span Ultrastructurally, there is extensive accumulation of autophagic vacuoles in many tissues including liver, pancreas, spleen, kidney and skeletal and heart muscle In hepatocytes, the autophagic degradation of long-lived proteins is severely impaired Cardiac myocytes are ultrastructurally abnormal and heart contractility is severely reduced These findings indicate that LAMP-2 is critical for autophagy This theory is further substantiated by the finding that human LAMP-2 deficiency causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes