Inter- and intrachromosomal rearrangements are both involved in the origin of 15q11-q13 deletions in Prader-Willi syndrome.
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Chromosomes, Human, Pair 15↗
Biomedical subjects
A Fois
Publications and source records attributed to A Fois.
Gastrointestinal disorders in muscular dystrophies.
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Gastrointestinal Diseases↗
Acute encephalitis due to human herpesvirus 6.
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DNA, Viral↗
Celiac disease with cerebral calcium and silica deposits: x-ray spectroscopic findings, an autopsy study.
An increased incidence of seizures and cerebral calcifications, usually bilateral and located in the occipital cortex, has been reported in celiac patients. The histology of cerebral lesions is not well defined, and their pathogenesis is only speculative. We report the autopsy results of a patient with celiac disease, seizures, and cerebral calcifications who died following a cerebral hemorrhage caused by Fisher-Evans syndrome. Calcifications were restricted to the cortical gray matter and composed of aggregates of small calcified spicules. Calcium deposition was present as psammoma-like bodies, along small vessels, and within neurons. X-ray spectroscopy of the calcified areas revealed that calcium (43%) and silica (57%) were present in the lesions. High silica content was also found in the cerebral hemorrhagic fluid. Silica toxicity has to be considered in regard to the pathogenesis of the cerebral lesions and of the seizures.
Autopsy↗
EEG, PET, SPET and MRI in intractable childhood epilepsies: possible surgical correlations.
Magnetic resonance imaging (MRI), single photon emission tomography (SPET), and positron emission tomography (PET) using [18F]fluorodeoxyglucose were used in combination with scalp and scalp-video EEGs in a group of 30 pediatric patients with drug resistant epilepsy (DRE) in order to identify patients who could benefit from neurosurgical approach. Seizures were classified according to the consensus criteria of The International League Against Epilepsy. In three patients infantile spasms (IS) were diagnosed; 13 subjects were affected by different types of generalized seizures, associated with complex partial seizures (CPS) in three. In the other 14 patients partial seizures, either simple (SPS) or complex, were present. A localized abnormality was demonstrated in one patient with IS and in three patients with generalized seizures. Of the group of 14 subjects with CPS, MRI and CT were normal in 7, but SPET or PET indicated focal hypoperfusion or hypometabolism concordant with the localization of the EEG abnormalities. In 5 of the other 7 patients anatomical and functional imaging and EEG findings were concordant for a localized abnormality. It can be concluded that functional imaging combined with scalp EEGs appears to be superior to the use of only CT and MRI for selecting children with epilepsy in whom a surgical approach can be considered, in particular when CPS resistant to therapy are present.
Brain↗
The molecular basis of canavan (aspartoacylase deficiency) disease in European non-Jewish patients.
Canavan disease is an infantile neurodegenerative disease that is due to aspartoacylase deficiency. The disease has been reported mainly in Ashkenazi Jews but also occurs in other ethnic groups. Determination of enzymatic activity for carrier detection and prenatal diagnosis is considered unreliable. In the present study, nine mutations were found in the aspartoacylase gene of 19 non-Jewish patients. These included four point mutations (A305E [39.5% of the mutated alleles], C218X [15.8%], F295S [2.6%], and G274R [5.3%]); four deletion mutations (827delGT [5.3%], 870del4 [2.6%], 566del7 [2.6%], and 527del6 [2.6%]); and one exon skip (527del108 [5.3%]). The A305E mutation is pan-European and probably the most ancient mutation, identified in patients of Greek, Polish, Danish, French, Spanish, Italian, and British origin. In contrast, the G274R and 527del108 mutations were found only in patients of Turkish origin, and the C218X mutation was identified only in patients of Gypsy origin. Homozygosity for the A305E mutation was identified in patients with both the severe and the mild forms of Canavan disease. Mutations were identified in 31 of the 38 alleles, resulting in an overall detection rate of 81.6%. All nine mutations identified in non-Jewish patients reside in exons 4-6 of the aspartoacylase gene. The results would enable accurate genetic counseling in the families of 13 (68.4%) of 19 patients, in whom two mutations were identified in the aspartoacylase cDNA.
Alleles↗
Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex.
Human pyruvate dehydrogenase (PDH)-complex deficiency is an inborn error of metabolism that is extremely heterogeneous in its presentation and clinical course. In a study of 14 patients (7 females and 7 males), we have found a mutation in the coding region of the E1 alpha gene in all 14 patients. Two female patients had the same 7-bp deletion at nt 927; another female patient had a 3-bp deletion at nt 931. Another female patient was found to have a deletion of exon 6 in her cDNA. Two other female patients were found to have insertions, one of 13 bp at nt 981 and one of 46 bp at nucleotide 1078. Two male patients were found to have a 4-bp insertion at nucleotide 1163. The remaining six patients all had missense mutations. A male patient and a female patient both had an A1133G mutation. The other missense mutations were C214T, C615A, and C787G (two patients). Five of these mutations are novel mutations, five have been previously reported in other patients, and two were published observations in other patients in an E1 alpha-mutation summary. In the four cases where parent DNA was available, only one mother was found to be a carrier of the same mutation as her child.
Base Sequence↗
Infantile spasms in patients with neurofibromatosis type 1.
The authors report two patients with neurofibromatosis type 1 who were affected by infantile spasms. The infantile spasms were severe and unresponsive to anticonvulsant treatment. The authors maintain that infantile spasms may belong to the clinical features of neurofibromatosis type 1.
Cerebral Ventricles↗
Vigabatrin treatment in children.
Sixty-nine children, aged from 2 months to 16 years and suffering from different types of drug-resistant epileptic seizures, mostly complex partial and secondary generalised, were recruited in an open, uncontrolled, prospective study of treatment with vigabatrin (gamma-vinyl GABA). Following a 3-month baseline observation period, the initial dose of vigabatrin of 10 mg/kg per day was progressively increased up to a maximum of 140 mg/kg per day, in addition to the conventional concomitant therapy. Sixteen patients showed a > or = 50% reduction in seizure frequency compared with the baseline, with complete control of seizures in nine cases. In 14 other patients, no substantial change in seizure frequency was observed, although an improvement in psychological performance after vigabatrin treatment warranted further continuation of the drug. In 35 patients vigabatrin was discontinued because of lack of efficacy (22 cases) and/or increased seizure frequency (13 cases). The clinical and biological tolerance of vigabatrin was remarkably good.
Adolescent↗
Celiac disease and epilepsy in pediatric patients.
Among 783 patients referred to our institute with different types of seizures as presenting symptom, systematic evaluation of antigliadin and antiendomysial antibodies in the serum has identified nine in whom jejunal biopsy has subsequently confirmed the diagnosis of celiac disease (CD). In three of them brain imaging showed the presence of calcified areas in the occipital region. They had complex partial seizures (CPS), associated in two with transient episodes of blindness. In another patient with CPS and generalized tonic-clonic seizures (GTCS) progressive multifocal cerebral calcifications were noted. In the other six patients with CPS and/or GTCS cerebral calcifications were absent. Symptoms of CD in all these cases were either not previously taken into account, or they were very mild or completely absent. In a group of 36 patients with clinically manifest CD, regular follow-up, and good compliance with the dietary regimen, no clinical seizures were reported. The pathogenetic mechanism and the relationship between epilepsy and an early diagnosis and treatment of celiac disease are discussed.
Adolescent↗
Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2-fluoro-2-deoxy-D-glucose and PET.
Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This finding suggests that the abnormalities seen on MRI are not due to defective blood supply, localised oedema, or grey matter heterotopic foci as previously hypothesised. The presence of the hypometabolic areas seems to be inconsistently related to the occurrence of seizures and is not proportional to the degree of mental impairment. This study provides evidence of a widespread cerebral hypometabolism that is not related to the presence of MRI abnormalities; conversely normal metabolism was present in the areas with an abnormal MRI signal.
Adolescent↗
Diagnosis of neurofibromatosis type 1 using RFLPs tightly linked to gene.
This study reports the results of a linkage analysis in nine families with members who had neurofibromatosis type 1 (NF1), using five restriction fragment length polymorphisms (RFLPs) tightly linked to the NF1 locus. The purpose of this analysis was to determine whether the at-risk individuals were carrying the NF1 allele and whether the nine families would be informative for prenatal testing. The families included 25 patients with NF1, 3 individuals at risk for NF1, and 11 unaffected subjects, with a total of 39 family members and 12 matings. In 6 matings two or more flanking probes were informative, in 3 matings only one probe was informative, and in the other 3 no probe was informative. DNA linkage analysis showed with more than 98% probability that the 3 at-risk individuals did not carry the NF1 mutation. No recombination events were observed. In 6 families it will be possible to do a DNA prenatal diagnosis if this type of test is requested. The NF1 gene has been identified and direct testing for the NF1 mutation is now possible. Linkage testing, however, will probably remain useful and complementary to direct analysis of the NF1 gene to reveal intragenic recombination events and for diagnosis in families in which the detection of mutation is difficult.
Adult↗
Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1.
We report the results of the reevaluation of 24 patients with neurofibromatosis type 1 (NF1) using central nervous system (CNS) imaging techniques. The first examination by computed tomography (CT) or magnetic resonance imaging (MRI) indicated the presence of optic glioma in three cases, "unidentified bright objects" (UBOs) in six, and a suspected right frontal tumor in one. In two patients optic glioma and UBOs were both present and in one of them a bulbar tumor was also suspected. Later imaging examinations revealed the appearance of optic glioma in three more cases and UBOs in nine. In two of these patients both optic glioma and UBOs were present. This study indicates that the likelihood of detecting imaging abnormalities in patients with NF1 increases when systematic follow-up is performed. Optic gliomas are characteristic of pediatric patients; they rarely give rise to clinical manifestations (1/6 cases) and in general progress very slowly. For these reasons, therapeutic strategy must be carefully considered and individually decided. UBOs are very frequent findings in pediatric patients with NF 1 and therefore they must be considered diagnostically relevant. They are not related to clinical manifestations and spontaneous regression has been observed. The nature of these imaging abnormalities is still unknown, but because they do not behave like tumors, useless and dangerous therapeutic procedures should not be employed.
Adolescent↗
Relationship between café-au-lait spots as the only symptom and peripheral neurofibromatosis (NF1): a follow-up study.
We re-examined 21 children with the possible diagnosis of peripheral neurofibromatosis (NF1) based on the presence of café-au-lait (CAL) spots as the single clinical finding. We evaluated whether "typical" or "atypical" appearance of the spots was important for the final diagnosis and whether the co-existence of other non-specific signs (e.g. pectus excavatum) were of any significance for the final diagnosis. In 8/14 (57.1%) cases with "typical" CAL spots, the diagnosis of NF1 was finally established on the basis of other criteria. For the other 6 patients the diagnosis is not yet definitive but highly probable on the basis of the presence of macrocephaly, pectus excavatum and/or MRI findings. Only one patient among five with "atypical" CAL spots possibly has NF1.
Brain Neoplasms↗
Epilepsy, progressive cerebral calcifications, and coeliac disease.
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Brain Diseases↗
Biochemical diagnosis of Canavan disease.
Canavan disease (CD) is a rare autosomal recessive disorder characterized by macrocephaly and progressive leukodystrophy. Up to now biopsy or necropsy were required to define the diagnosis. Recently the disease has been related to N-acetylaspartic aciduria and deficiency of aspartoacylase, an enzyme possibly involved in the myelin synthesis. These biochemical findings have provided a diagnostic marker for the disease. We report a new case of infantile CD in which the demonstration of N-acetylaspartic aciduria and a marked deficiency of aspartoacylase activity confirmed the diagnosis.
Amidohydrolases↗
Molecular study in von Recklinghausen neurofibromatosis (NF1).
The von Recklinghausen neurofibromatosis (NF1) gene has been mapped to the pericentromeric region of chromosome 17 and various DNA markers have been identified in this region. We have performed a genetic analysis using an anonymous DNA marker, HHH202 (D17S33), tightly linked to the NF1 gene in seven NF1 Italian families. Only one family was fully informative for the HHH202/RsaI polymorphism. In this family this marker can be used for presymptomatic and prenatal diagnosis. However, it is necessary to use additional flanking markers in order to increase informativeness and to obtain better diagnostic accuracy.
Female↗