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F Mari

Publications and source records attributed to F Mari.

At least 19 recordsLinked to original sources
PubMed2007

The Italian XLMR bank: a clinical and molecular database.

Mental retardation (MR) is a nonprogressive condition characterized by a significant impairment of intellectual capabilities with deficit of cognitive and adaptive functioning and onset before 18 years. Mental retardation occurs in about 2 to 3% of the general population and it is estimated that 25 to 35% of the cases may be due to genetic causes. Among these "genetic" MR, 25 to 30% are probably due to mutations in a gene on the X chromosome (X-linked mental retardation, XLMR). Given the genetic heterogeneity of XLMR, the availability of a considerable number of patients with accurate phenotypic classification is a crucial factor for research. The X-linked Mental Retardation Italian Network, which has been active since 2003, has collected detailed clinical information and biological samples from a vast number of MR patients. Collected samples and clinical information are inserted within the XLMR bank, a comprehensive molecular and clinical web-based database available at the address http://xlmr.unisi.it. The database is organized in three distinct parts. Part I and II contain several electronic schedules to register information on the family, the phenotypic description, the photographs, and a 20 sec movie of the patient. Part III allows the registration of molecular analyses performed on each case; samples and clinical data are usable via password-restricted access. Clinical and molecular centers interested in joining the network may request a password by simply contacting the Medical Genetics of the University of Siena. The XLMR bank is an innovative biological database that allows the collection of molecular and clinical data, combines descriptive and iconographic resources, and represents a fundamental tool for researchers in the field of mental retardation.

Computer Security↗
PubMed2006

2q24-q31 deletion: report of a case and review of the literature.

We report a patient with a de novo interstitial deletion of the long arm of chromosome 2 involving bands 2q24.3-q31.1. The patient shows postnatal growth retardation, microcephaly, ptosis, down-slanting palpebral fissures, long eyelashes and micrognathia. Halluces are long, broad and medially deviated, while the other toes are laterally deviated and remarkably short with hypoplastic phalanges. She also showed developmental delay, seizures, lack of eye contact, stereotypic and repetitive hand movements and sleep disturbances with breath holding. Prenatal and three independent postnatal karyotypes were normal. Array-CGH analysis allowed us to identify and characterize a "de novo" 2q interstitial deletion of about 10.4Mb, involving segment between cytogenetic bands 2q24.3 and 2q31.1. The deletion was confirmed by quantitative PCR. About 30 children with 2q interstitial deletion have been reported. The deletion described here is overlapping with 15 of these cases. We have attempted to compare the clinical features of our patient with 15 overlapping cases. The emerging phenotypes include low birth weight, postnatal growth retardation, mental retardation and developmental delay, microcephaly, and peculiar facial dysmorphisms. Peculiar long and broad halluces with an increased distance between the first and the second toe are ("sandal gap" sign) present in most of the described patients. The gene content analysis of the deleted region revealed the presence of some genes that may be indicated as good candidates in generating both neurological and dysmorphic phenotype in the patient. In particular, a cluster of SCNA genes is located within the deleted region and it is known that loss of function mutations in SCNA1 gene cause a severe form of epilepsy.

Abnormalities, Multiple↗
PubMed2006

Use of levetiracetam in treating epilepsy associated with other medical conditions.

OBJECTIVE: This prospective, open-label study was conducted to evaluate the effectiveness, tolerability, and safety of levetiracetam in patients with epilepsy in whom unfavorable metabolism, complex drug interactions, or direct toxic effects of antiepileptic drugs (AEDs) had caused a worsening of comorbid conditions. METHODS: Study design included the introduction of levetiracetam, discontinuation of other AEDs, and a serial assessment comprising electroencephalograms and blood tests at baseline and 2, 6, and 12 months. Of 21 patients, 16 had partial and five generalized epilepsy. Concomitant pathologies were gastroenterological (six), vascular (four), endocrinological (four), or complex conditions including hematological (four) or dermatological (three) disease. A change of regimen was necessitated by drug-drug interactions in four patients, direct real or potential toxic effects of previous AEDs in 13, and a combination of interactions/toxic effects in four. RESULTS: After 12 months, 12 patients were seizure-free, nine had reductions in seizure frequency of 50-75%, and improvement in concomitant medical conditions was observed. No side effects were reported. CONCLUSION: Levetiracetam appears to be effective, well tolerated, and safe in patients with epilepsy and other medical conditions that are difficult to manage because of drug interactions or AED-related side effects.

Adolescent↗
PubMed2005

Non-syndromic X-linked mental retardation: from a molecular to a clinical point of view.

This review focuses on the 19 identified genes involved in X-linked "non-syndromic" mental retardation (MR) and defines the signaling pathways in which they are involved, focusing on emerging common mechanisms. The majority of proteins are involved in three distinct pathways: (1) Rho GTPases pathway modulating neuronal differentiation and synaptic plasticity; (2) Rab GTPases pathway regulating synaptic vesicle cycling; (3) gene expression regulation. The function of four proteins (ACSL4, AT2, SLC6A8, and SAP102) could not be reconciled to a common pathway. From a clinical point of view, the review discusses whether some common dysmorphic features can be identified even in non-syndromic MR patients and whether it is correct to maintain the distinction between "non-syndromic" and "syndromic" MR.

Chromosomes, Human, X↗
PubMed2005

Germline mosaicism in Rett syndrome identified by prenatal diagnosis.

Rett syndrome is an X-linked neurodevelopmental dominant disorder that affects almost exclusively girls. The vast majority of cases are sporadic and are caused by de novo mutations in the MECP2 gene, located in Xq28. Only few familial cases have been reported: in four cases, the mother was an asymptomatic carrier and in other four cases, the germline mosaicism in the mother was postulated. Owing to the above reported cases of germline mosaicism, we decided to offer prenatal diagnosis to all expectant mothers with a Rett daughter despite the absence of the causative mutation in parents' blood. We describe here the outcome of the first nine cases of prenatal diagnosis followed by our center. In eight cases, the fetus did not carry the mutation. In one case, the female fetus did carry the same mutation of the affected sister. The couple decided to interrupt the pregnancy and to devolve fetal tissues for research purposes. Our results indicate that prenatal diagnosis should be proposed to all couples with a Rett daughter, even when the mutation is apparently de novo. Moreover, one positive prenatal test among the first nine cases indicates that germline mosaicism may be seriously considered for the assessment of recurrence risk during genetic counseling.

Adult↗
PubMed2005

CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms.

BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder, almost exclusively affecting females and characterised by a wide spectrum of clinical manifestations. Both the classic form and preserved speech variant of Rett syndrome are due to mutations in the MECP2 gene. Several other variants of Rett syndrome have been described. In 1985, Hanefeld described a variant with the early appearance of convulsions. In this variant, the normal perinatal period is soon followed by the appearance of seizures, usually infantile spasms. We have observed two patients with signs of Rett syndrome showing acquired microcephaly and stereotypic midline hand movements. The disease started with generalised convulsions and myoclonic fits at 1.5 months in the first patient and with spasms at 10 days in the other, suggesting a diagnosis of the Hanefeld variant. In these patients, MECP2 point mutations and gross rearrangements were excluded by denaturing high performance liquid chromatography and real time quantitative PCR. The ARX and CDKL5 genes have been associated with West syndrome (infantile spasms, hypsarrhythmia, and mental retardation). METHODS: Based on the clinical overlap between the Hanefeld variant and West syndrome, we analysed ARX and CDKL5 in the two girls. RESULTS: We found frameshift deletions in CDKL5 in both patients; one in exon 5 (c.163_166delGAAA) and the other in exon 18 (c.2635_2636delCT). CDKL5 was then analysed in 19 classic Rett and 15 preserved speech variant patients, all MECP2 negative, but no mutations were found. CONCLUSION: Our results show that CDKL5 is responsible for a rare variant of Rett syndrome characterised by early development of convulsions, usually of the spasm type.

Amino Acid Sequence↗
PubMed2004

Mitochondrial abnormalities in genetically assessed oculopharyngeal muscular dystrophy.

We report a family with a clinical diagnosis of oculopharyngeal muscular dystrophy in which muscle biopsy showed mitochondrial changes such as cytochrome-c-oxidase-negative fibers and aggregates of mitochondria containing paracrystalline inclusions. Molecular analysis demonstrated a GCG expansion in the poly(A)-binding protein 2 (PABP2) gene and failed to demonstrate multiple deletions of mtDNA. We hypothesize that mitochondrial abnormalities may be a secondary phenomenon. This observation may suggest that the PABP2 gene could interfere in the posttranscriptional regulation of genes involved in mitochondrial function.

Adult↗
PubMed2003

Neurological presentation of Ehlers-Danlos syndrome type IV in a family with parental mosaicism.

Ehlers-Danlos syndrome type IV (EDS-IV) is an autosomal-dominant disorder caused by a defect of type III collagen which leads to ruptures of arteries and hollow organs. Neurological presentation with muscle involvement and flexion contractures of the finger joints is uncommon. We clinically characterized seven members of a family with EDS-IV. The index patient, a young woman with an acrogeric face, suffered chronic muscle pain and cramps, Achilles tendon retraction, finger flexion contractures and seizures. The mother had similar features and had experienced an ischemic stroke. Biochemical study in cultured fibroblasts and molecular analysis of the COL3A1 gene led to the diagnosis of EDS-IV. A glycine substitution, p.G883V, within the triple helix of the alpha 1(III) chain, was found in the index patient and in the mother. The maternal grandfather and an aunt each had an abdominal aortic aneurysm, the rupture of which was the cause of death in the latter, at 40 years of age. Surprisingly, we found the mutation, as a mosaic, in the asymptomatic maternal grandmother. This expands the clinical spectrum of EDS type IV and confirms that in some families mosaicism can be identified as the source of the mutation.

Adult↗
PubMed2003

Chromosome 2 deletion encompassing the MAP2 gene in a patient with autism and Rett-like features.

We present here a unique case of a 14-year-old female with autism and some features similar to Rett syndrome (RTT). Genetic analysis demonstrated a large deletion of chromosome 2q instead of a MECP2 mutation. Like a Rett patient, she is dyspraxic and shows frequent hand-washing stereotypic activities, hyperpnea, and bruxism. Like a preserved speech variant (PSV) of RTT, she is obese, able to speak in second and third persons, frequently echolalic, and has final normal head circumference and autistic behavior. In addition, she has dysmorphic features such as down-slanting palpebral fissures, low set ears without lobuli, bilateral flat feet, and bilateral syndactyly of the second and third toes, which do not belong to the Rett spectrum. She has a de novo chromosomal deletion in 2q34 of paternal origin. Gene content analysis of the deleted region showed the presence of 47 genes (14 putative and 33 known genes). This region contains some interesting genes such as ADAM23/MDC3, CREB1, KLF7, and MAP2. Because alteration of neuronal maturation, dendritic anomalies, and a decrease in MAP2 immunoreactivity in white matter neurons are well documented in RTT patients, we propose MAP2 gene as a good candidate for the generation of PSV phenotype in this case.

Adolescent↗
PubMed2001

PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation.

Congenital aniridia is due to deletions and point mutations in the PAX6 gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the PAX6 locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. Mutation screening of the PAX6 gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family.

Abnormalities, Multiple↗
PubMed2000

A mutation in the rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males.

Heterozygous mutations in the X-linked MECP2 gene cause Rett syndrome, a severe neurodevelopmental disorder of young females. Only one male presenting an MECP2 mutation has been reported; he survived only to age 1 year, suggesting that mutations in MECP2 are male lethal. Here we report a three-generation family in which two affected males showed severe mental retardation and progressive spasticity, previously mapped in Xq27.2-qter. Two obligate carrier females showed either normal or borderline intelligence, simulating an X-linked recessive trait. The two males and the two obligate carrier females presented a mutation in the MECP2 gene, demonstrating that, in males, MECP2 can be responsible for severe mental retardation associated with neurological disorders.

Adult↗
PubMed1998

Isolation of parvalbumin isotypes by preparative HPLC techniques.

Parvalbumins are highly stable Ca2+ binding proteins, present in large quantities in the sarcoplasmic reticulum in the white muscle of most lower vertebrates and fish. The properties of these proteins make them promising antigens for the use as a specific biomarker for fish species identification. Parvalbumin isotypes were isolated, on a preparative scale level, by use of size exclusion chromatography (SEC) and anion exchange HPLC. The utility of this technique, with regard to maximizing purified isotypes, is discussed.

Animals↗
PubMed1997

Predictive value of clinical indices in detecting aspiration in patients with neurological disorders.

OBJECTIVES: (1) To evaluate the predictive value of a detailed clinical screening of aspiration in patients with neurological diseases, both with and without symptoms of dysphagia taking videofluoroscopy as the gold standard; (2) to assess the existence of risk factors for silent aspiration, measuring the cost-benefit ratio of radiological examination. METHODS: 93 consecutive patients meeting the diagnostic criteria for a neurological disease with a risk of swallowing dysfunctions (cerebrovascular accidents, brain injury, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, myotonic dystrophy, and abiotrophic diseases) underwent a detailed clinical assessment using a 25 item form to check for symptoms of dysphagia and impairment of the oropharyngeal swallowing mechanism. The 3 oz water swallow test was also performed to assess the aspiration risk. Sensitivity, specificity, positive predictive, and negative predictive values (NPV) of dysphagia, history of cough on swallowing, and 3 oz test positivity, versus videofluoroscopy documented aspiration, taken as the gold standard, were measured in all the patients and in subgroups with different neurological disorders. RESULTS: Non-specific complaints of dysphagia showed a very poor predictive value, whereas the symptom "cough on swallowing" proved to be the most reliable in predicting the risk of aspiration, with 74% sensitivity and specificity, 71% positive predictive, and 77% negative predictive value. The standardised 3-oz test had a higher predictive potential than the clinical signs, but had low sensitivity. The association of cough on swallowing with the 3 oz test gave a positive predictive of 84%, and an negative predictive value of 78%. In cases where the clinical tests failed to detect any impairment, videofluoroscopy documented only a low risk (20%) for mild aspiration. CONCLUSIONS: The association of two clinical items (such as history of cough on swallowing and 3 oz test positivity) provides a useful screening tool, the cost:benefit ratio of which seems very competitive in comparison with videofluoroscopy in aspiration risk evaluation.

Adolescent↗
PubMed1996

Influence of vigabatrin on cognitive performances and behaviour in patients with drug-resistant epilepsy.

INTRODUCTION: The aim of this research was to evaluate changes in cognitive performances, mood and quality of life in drug-resistant epileptic patients, after the introduction of Vigabatrin (VGB) as additional treatment. MATERIAL AND METHODS: A four-step evaluation was carried out in two groups of 20 patients each, randomly assigned to VGB or placebo treatment. A battery of neuropsychological tests investigating attention, memory and adaptive abilities, associated with inventories concerning depression, quality of life and the concern of families upon patient behaviour, were utilised. For each subject, four evaluations were performed, two before and two after VGB/placebo administration. RESULTS: No relevant side-effects regarding cognition and behavior were detected in the VGB group. The intra-group comparison between pre- and post-treatment phases showed a slight improvement in cognitive performances of VGB patients and a positive change in their overall psychological status. The inter-group comparison confirmed the selective improvement occurring in the trend of a few neuropsychological test scores in the VGB group. CONCLUSION: Such results help to reject the hypothesis that the addition of VGB to the current antiepileptic treatment may affect cognitive performances and behaviour.

Adolescent↗
PubMed1996

[Aneurysms of the popliteal artery. Our experience apropos of 37 cases].

The authors describe their experience concerning the surgical treatment of aneurysmatic pathology of the popliteal artery. This is the most frequent site for aneurysm after aortic aneurysm. Since 1979 to 1994, 26 patients, 21 men and 5 women (mean age 65.8 years), have been treated at the Institute of Clinical Surgery of the University of Ferrara for a total of 37 popliteal aneurysms. Thirteen patients had more than one aneurysm. Before the operation, all patients underwent DSA, and echo Doppler, 7 with CAT and 4 with RMN. Twenty-nine substitutions, 7 by passes and 1 ligation were performed. Twelve of the 29 substitutions were made by reversed saphenous vein. Fourteen by PTFEe, and 3 by dacron. In 4 cases it was necessary to reimplant either the anterior tibial artery (3 cases) or the posterior tibial artery (1 case) separately. The results obtained were good especially in the post-trauma patients. Only 3 amputations were necessary due to graft obstruction immediately after surgery, and in post-traumatic conditions.

Aged↗