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INTRODUCTION: Attention and working memory are key cognitive functions that allow us to select and maintain information in our mind for a short time, being essential for our daily life and, in particular, for learning and academic performance. It has been shown that musical training can improve working memory performance, but it is still unclear if and how the neural mechanisms of working memory and particularly attention are implicated in this process. In this work, we aimed to identify the oscillatory signature of bimodal attention and working memory that contributes to improved working memory in musically trained children. MATERIALS AND METHODS: We recruited children with and without musical training and asked them to complete a bimodal (auditory/visual) attention and working memory task, whereas their brain activity was measured using electroencephalography. Behavioral, time-frequency, and source reconstruction analyses were made. RESULTS: Results showed that, overall, musically trained children performed better on the task than children without musical training. When comparing musically trained children with children without musical training, we found modulations in the alpha band pre-stimuli onset and the beginning of stimuli onset in the frontal and parietal regions. These correlated with correct responses to the attended modality. Moreover, during the end phase of stimuli presentation, we found modulations correlating with correct responses independent of attention condition in the theta and alpha bands, in the left frontal and right parietal regions. CONCLUSIONS: These results suggest that musically trained children have improved neuronal mechanisms for both attention allocation and memory encoding. Our results can be important for developing interventions for people with attention and working memory difficulties.

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BACKGROUND: Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling. DEVELOPMENT: This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS). CONCLUSIONS: Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments.

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Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and co-morbid autism. It is caused by an amplification of the CGG repeat (>200), which is known as the full mutation, within the 5'UTR of the FMR1 gene. Expansions between 55-200 CGG repeats are termed premutation and are associated with a greater risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated premature ovarian insufficiency. Intermediate alleles, also called the grey zone, include approximately 45-54 repeats and are considered borderline. Individuals with less than 45 repeats have a normal FMR1 gene. We report the occurrence of CGG expansions of the FMR1 gene in Chile among patients with ID and families with a known history of FXS. Here, we present a retrospective review conducted on 2321 cases (2202 probands and 119 relatives) referred for FXS diagnosis and cascade screening at the Institute of Nutrition and Food Technology (INTA), University of Chile. Samples were analysed using traditional cytogenetic methods and/or PCR. Southern blot was used to confirm the diagnosis. Overall frequency of FMR1 expansions observed among probands was 194 (8·8%), the average age of diagnosis was 8·8 ± 5·4 years. Of 119 family members studied, 72 (60%) were diagnosed with a CGG expansion. Our results indicated that the prevalence of CGG expansions of the FMR1 gene among probands is relatively higher than other populations. The average age of diagnosis is also higher than reference values. PCR and Southern blot represent a reliable molecular technique in the diagnosis of FXS.

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Carriers of an FMR1 premutation allele (55-200 CGG repeats) often develop the neurodegenerative disorders, fragile X-associated tremor/ataxia syndrome (FXTAS). Neurological signs of FXTAS, parkinsonism and rapid onset of cognitive decline have not been reported in individuals with an unmethylated full mutation (FM). Here, we report a Chilean family affected with FXS, inherited from a parent carrier of an FMR1 unmethylated full mosaic allele, who presented with a fast progressing FXTAS. This case suggests that the definition of FXTAS may need to be broadened to not only include those with a premutation but also those with an expanded allele in FM range with a lack of methylation leading to elevated FMR1-mRNA expression levels and subsequent RNA toxicity.

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BACKGROUND: Chromosome aberrations (CA) are the main etiology of multiple congenital malformations, recurrent abortions and intellectual disability (ID) specifically of moderate and severe degree. They account for 0.3 to 1% of newborns (NB) and 6 of 10,000 NB have chromosome imbalances with submicroscopic deletions or duplications smaller than 10 MB that are overlooked by conventional cytogenetic studies. AIM: To report the results of cytogenetic and molecular studies performed in patients with a congenital malformation disease or ID with or without dysmorphic features, attended in a regional hospital. PATIENTS AND METHODS: One hundred and eighty patients, 27 with a clinical diagnosis of Down syndrome, derived for the suspicion of a genetic disease, were studied. A karyogram was performed in all of them and in 30 cases additional molecular studies, such as fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) were carried out. RESULTS: Among the 153 patients without Down syndrome, 20 (13%) had a genetic abnormality responsible for the altered phenotype. Sixteen had a chromosome aberration (structural and numerical aberrations in 75 and 25% respectively) and four had genetic molecular alterations. Additional studies were performed to confirm or better characterize the chromosome aberration in 13 of the 30 patients in whom these were requested. CONCLUSIONS: Chromosome and specific genetic molecular studies in selected cases help to characterize patients with genetic diseases. The collaboration between academic and health care facilities is crucial.

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Background: Chromosome aberrations (CA) are the main etiology of múltiple congenital malformations, recurrent abortions and intellectual disability (ID) specifically of modérate and severe degree. They accountfor 0.3 to 1 percent of newborns (NB) and 6 of 10,000 NB have chromosome imbalances with submicroscopic deletions or duplications smaller than 10 MB that are overlooked by conventional cytogenetic studies. Aim: To report the results of cytogenetic and molecular studies performed in patients with a congenital malformation disease or ID with or without dysmorphic features, attended in a regional hospital. Patients and Methods: One hundred and eighty patients, 27 with a clinical diagnosis ofDown syndrome, derivedfor the sus-picion of a genetic disease, were studied. A karyogram was performed in all ofthem and in 30 cases additional molecular studies, such as fluorescence in situ hybridization (FISH) orpolymerase chain reaction (PCR) were carried out. Results: Amongthe 153 patients without Down syndrome, 20 (13 percent) had a genetic abnormality responsible for the altered phenotype. Sixteen had a chromosome aberration (structural and numerical aberrations in 75 and 25 percent respectively) andfour had genetic molecular alterations. Additional studies were performed to confirm or better characterize the chromosome aberration in 13 ofthe 30 patients in whom these were requested. Conclusions: Chromosome and specific genetic molecular studies in selected cases help to characterize patients with genetic diseases. The collaboration between academic and health care facilities is crucial.

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Background: Mental retardation or intellectual disability affects 2 percent ofthe general population, but in 60 percent to 70 percent of cases the real cause ofthis retardation is not known. An early etiologic diagnosis of intellectual disability can lead to opportunities for improved educational interventions, reinforcing weak aáreas and providing a genetic counseling to the family Aim: To search genetic diseases underíying intellectual disabilities of children attending a special education school. Material and methods: A clinical geneticist performed the history and physical examination in one hundred and three students aged between 5 and 24 years (51 males). A blood sample was obtained in 92 of them for a genetic screening that included a standard karyotype, fragile X molecular genetic testing and search for inborn errors of metabolism by tándem mass spectrometry. Results: This approach yielded an etiological diagnosis in as much as 29 patients. Three percent of them had a fragile X syndrome. Inborn errors of metabolism were not detected. Conclusions: This type of screening should be done always in children with intellectual disability to establish an etiological diagnosis.

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OBJECTIVE: We assessed the impact of high serum folate concentration on erythrocyte S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) concentrations, SAM/SAH ratio, CpG methylation levels across the promoter region of the extracellular superoxide dismutase (ec-SOD) gene, and ec-SOD activity in healthy men. METHODS: Serum folate levels were measured in 111 subjects who were categorized in quintiles according to their folate status. Subjects located at the lowest, middle, and upper quintiles were selected for assessment of SAM and SAH by high-performance liquid chromatography, C677T genotype of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, ec-SOD methylation of CpG sites in lymphocytes genomic DNA by bisulfate treatment, and ec-SOD activity by a chemical assay. RESULTS: Sixteen subjects were in the lowest serum folate quintile (<23.6 nmol/L), 17 in the middle (>34-<42 nmol/L), and 14 in the highest (>45nmol/L). SAM concentration was higher in the upper than in the middle and lowest quintiles (5.57 +/- 1.58, 2.52 +/- 0.97, 2.29 +/- 1.2 micromol/L; P < 0.0001). SAH concentration was higher in the upper compared with the lowest quintile (0.76 +/- 0.24 versus 0.52 +/- 0.23 micromol/L, P < 0.001). There were no differences in the SAM/SAH ratio, ec-SOD activity, methylation status of CpG sites of the ec-SOD gene, and TMTHFR C677T genotype between groups. CONCLUSION: Serum folate concentrations in the highest quintile among healthy humans are associated with increased erythrocyte SAM and SAH concentrations, but not with SAM/SAH ratio or with methylation levels of CpG sites across the promoter region of the ec-SOD gene. Further research is required to determine if these findings are beneficial or harmful.

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BACKGROUND: Mental retardation or intellectual disability affects 2% of the general population, but in 60% to 70% of cases the real cause of this retardation is not known. An early etiologic diagnosis of intellectual disability can lead to opportunities for improved educational interventions, reinforcing weak areas and providing a genetic counseling to the family. AIM: To search genetic diseases underlying intellectual disabilities of children attending a special education school. MATERIAL AND METHODS: A clinical geneticist performed the history and physical examination in one hundred and three students aged between 5 and 24 years (51 males). A blood sample was obtained in 92 of them for a genetic screening that included a standard karyotype, fragile X molecular genetic testing and search for inborn errors of metabolism by tandem mass spectrometry. RESULTS: This approach yielded an etiological diagnosis in as much as 29 patients. Three percent of them had a fragile X syndrome. Inborn errors of metabolism were not detected. CONCLUSIONS: This type of screening should be done always in children with intellectual disability to establish an etiological diagnosis.

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BACKGROUND: Several population studies have shown that patients with neural tube defects (NTD), have a higher frequency of a genetic mutation related with thermolability of the enzyme 5,10-metylentetrahydrofolate reductase (MTHFR). There are regional and ethnic variations in the genotypic or allelic frequency of this mutation and its possible relationship with NTD and others congenital anomalies. AIM: To estimate the frequency of the C677T polymorphism of MTHFR in control women and mothers of spina bifida cases. PATIENTS AND METHODS: We analyzed 58 blood samples from mothers who had a child diagnosed with spina bifida. A group of 184 healthy mothers matched by age and with no NTD offspring served as controls. We determined the C677T polymorphism on the MTHFR gene by means of PCR and the analysis of the digestion pattern of HinfI restriction enzyme. RESULTS: The genotypic frequencies showed concordance with Hardy-Weinberg equilibrium, in controls (p = 0.35), and in mothers of the cases (p = 0.95). The odds ratio to the TT genotype compared with the CC genotype (reference category) was estimated as 1.54 (IC 95%: 0.66-3.61), while the odds ratio for the TC genotype compared with CC genotype was 1.06 (IC 95%: 0.48-2.33). CONCLUSION: No differences in the C677T polymorphism of the MTHFR were observed between mothers who had a child diagnosed with spina bifida and control mothers.

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BACKGROUND: The diagnosis of Prader-Willi and Angelman syndromes is difficult, since their phenotypic manifestations are variable and unspecific. The study of the methylation state of DNA in 15(q11-q13) using polymerase chain reaction, called methylation test, allows the diagnosis of most patients with Prader-Willi and Angelman syndromes, irrespective if the underlying molecular alteration is a deletion, uniparental disomy or a punctual imprinting mutation. AIM: To assess the effectiveness of methylation test in the diagnosis of Prader-Willi and Angelman syndromes. PATIENTS AND METHODS: Thirty seven cases with a presumptive diagnosis of Prader-Willi syndrome and 25 with the presumptive diagnosis of Angelman syndrome were studied. Methylation test was done in genomic DNA obtained from peripheral lymphocytes. RESULTS: Methylation test confirmed the clinical diagnosis in 11 of 37 patients with Prader Willi (30%) and 6 of 25 patients with Angelman syndrome (24%). CONCLUSIONS: Clinical criteria overestimate the diagnosis of Prader-Willi and Angelman syndromes. The initial diagnosis should be confirmed with the methylation test and, if necessary, with FISH that will detect most deletions in the region.

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BACKGROUND: The unequivocal diagnosis of fragile Xq syndrome is based in the direct analysis of the underlying FMR-1 gene mutation, that consists in an increased number of trinucleotide CGG repetitions. AIM: To study families with fragile Xq syndrome, using the Southern technique for the analysis of the mutation. SUBJECTS AND METHODS: Fifteen individuals, pertaining to 6 families with fragile Xq syndrome, were studied. Clinical, cytogenetic and molecular analysis using Southern technique, were done. RESULTS: Five male individuals had a clinically evident syndrome, confirmed by cytogenetic analysis that showed fragility in 10 to 29% of studied cells. One subject with a clinical picture suggesting fragile Xq had a normal cytogenetic study. The other studied subjects were the mothers of the five subjects with the syndrome, that must be carriers, and four brothers. Molecular analysis showed that seven subjects (5 males) had a complete mutation, five (4 females) were carriers of a pre mutation and three (2 males) did not have the mutation. CONCLUSIONS: The Southern technique allows to verify the normal condition of FRAXA locus, identify carriers and to detect complete mutations in fragile Xq syndrome.

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In order to describe the frequency of non classical forms of 21 trisomy in patients with Down's syndrome at the cytogenetic's laboratory of our institution (Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile) 201 chromosomal studies from peripheral blood lymphocytes of patients referred with a clinical diagnosis of Down's syndrome were analyzed. Among them 22 (11%) cases showed no chromosomal abnormalities, 161 (80%) had classic 21 trisomy, 7 (3.5%), showed 21 trisomy by translocation, 5 (2.5%) had 21 trisomy mosaicism, 6 (3%) showed 21 trisomy plus an autosomic balanced translocation. Male to female rate was 1.18:1 and diagnosis was done at the neonatal period in 26.8% of cases. Early recognition of the different kinds of chromosomal abnormalities in Down's syndrome is important if appropriate genetic council is the goal.

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PIP: This work describes a study of factors determining the acceptability of the ovulation method of family planning conducted at the Natural Methods Clinic of the University of Chile Hospital's Department of Obstetrics and Gynecology. Persons desiring instruction concerning natural family planning complete a questionnaire, hear an introductory talk which stresses the Billings method, and receive personal instruction in modular units. Multiple factors were studied for both acceptance of registration and acceptance of the course. Entrance into the course constituted acceptance of registration, and achievement of the status of dependent users constituted acceptance of the instruction phase. 147 of the 224 couples registering in the natural family planning clinic between November 1981-August 1983 began the course of instruction, and 96 subsequently adopted the method. 42.9% of the original 224 couples thus became dependent users. A significantly positive statistical association with registration was found for 73 factors. 4 separate elements of acceptability were measured: predictive value, acceptability rate, sensitivity, and frequency. The ideal factors in terms of acceptability would have positive values on all 4 dimensions nearing 100%. The most important factors identified in the study in the phase of registration and their measures for predictive value, frequency, sensitivity, and rate of acceptability respectively were: both partners shared the decision to try the method (71%, 75%, 90%, and 53%), the method is not harmful (71%, 75%, 90%, and 53%), the male understands the basics of the method (71%, 73%, 89%, and 52%), the woman understood the functioning of natural methods (70%, 57%, 66%, and 40%). All the above factors are modifiable through information and education. Statistically significant associations were found for only 16 factors in the phase of instruction. The most important factors were that both partners had previous knowledge of the method and had no prior experience with the IUD. The predictive power of the acceptability factors varied from 17%-80% for the registration phase and from 38%-81% for the instruction phase.^ieng

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Previous studies have claimed that the Chilean matorral is more open than the Califonia chaparral, and have attributed this dissimilarity largely to the role of man in Chile. In this paper we show that in general the Chilean matorral has a structure better described as shrub clumps that merge to form a continuous vegetation matrix only in very mesic habitats, where it is comparable to the Califonia chaparral. We also present evidence that these clumps have been present for at least the last 26 years and that even without human disturbance they are likely to maintain themselves. Evidence for the latter pertains to seed dispersal, seed germination and establishment, seedling survival, and the diameter size structure of shrub clumps. Finally, we propose that differences between the California chaparral and Chilean matorral are more profound than previously thought and are due not only to different degrees of human disturbance, but also to the presence of periodical natural fires in California and not in Chile, and to different shrub recruitment patterns and mammalian herbivore activity in the two areas.

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Interactions between vegetative growth and reproduction were evaluated in Peumus boldus, Lithraea caustica and Laretia acaulis, three woody dioecious species in central Chile. Phenological observations were made periodically on marked branches of male and female plants, and biomass allocation (dry weight) to vegetative and reproductive tissues was measured. The magnitude of flowering was evaluated in groups of plants in three successive seasons. The patterns of activities are species- and sex-dependent, and cycles of 2-4 years have been established. Branches that produce flowers either do not grow or grow less than branches without flowers, and males and females have differential resource allocation: male branches attain higher biomass values. Groups of plants show seasonal behavior that suggest synchrony in their reproductive activities.