Identifying Genetic Etiology in Patients with Intellectual Disability: An Experience in Public Health Services in Northeastern Brazil.

Intellectual disability (ID) is considered a common neuropsychiatric disorder that affects up to 3% of the population. The etiologic origin of ID may be genetic, environmental, and multifactorial. Chromosomopathies are relatively common among the genetic causes of ID, especially in the most severe cases and those associated with dysmorphic features. Currently, the application of new molecular cytogenetics technologies has increasingly allowed the identification of microdeletions, microduplications, and unbalanced translocations as causes of ID. The objective of this study was to investigate the etiology of ID in patients admitted to a public hospital in Northeastern Brazil. In total, 119 patients with ID who had normal karyotypes and fragile X exams participated in this study. The patients were initially physically examined for microdeletion syndromes and then tested using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), methylation-sensitive polymerase chain reaction (MS-PCR), and chromosome microarray analysis (CMA), according to clinical suspicion. Patients with no diagnoses after FISH, MLPA, and/or MS-PCR evaluations were subsequently tested by CMA. The rate of etiologic diagnoses of ID in the current study was 28%. FISH diagnosed 25 out of 79 tested (31%), MLPA diagnosed 26 out of 79 tested (32%), MS-PCR diagnosed 7 out of 20 tested (35%), and the single nucleotide polymorphism array diagnosed 6 out of 27 tested (22%). Although the CMA is the most complete and recommended tool for the diagnosis of microdeletions, microduplications, and unbalance translocations in patients with ID, FISH, MLPA, and MS-PCR testing can be used as the first tests for specific syndromes, as long as the patients are first physically screened clinically, especially in the public health networks system in Brazil, where resources are scarce.

Case of 15q26-qter deletion associated with a Prader-Willi phenotype.

Prader-Willi syndrome (PWS) is one of the common neurogenetic disorders associated with intellectual disability. PWS involves a complex inheritance pattern and is caused by an absence of gene expression on the paternally inherited 15q11.2-q13 region, either due to deletion, maternal uniparental disomy or imprinting defect. The syndrome is characterized principally by severe neonatal hypotonia, a weak suck in infancy that is later followed by hyperphagia and obesity, developmental delay, intellectual disability and short stature. In the case of the chromosome 15q26-qter deletion syndrome or Drayer's syndrome, very few reports have been published. Its characteristics include intrauterine growth restriction, postnatal growth failure, varying degrees of intellectual disability, developmental delay, typical facial appearance and diaphragmatic hernia. The present paper describes a female patient in whom clinical findings were suggestive of PWS and deletion in the 15q26-qter region. Both karyotyping and methylation-specific polymerase chain reaction were shown to be normal. Nevertheless, fluorescence in situ hybridization showed a 15qter deletion that was later mapped by single nucleotide polymorphism (SNP)-array. The deleted genomic region involves the insulin-like growth factor-1 receptor (IGF1R) gene, which is related to short stature, developmental delay and intellectual disability. This case had various clinical characteristics in common with the cases of 15q26-qter deletionand characteristics compatible with PWS.

A modified MS-PCR approach to diagnose patients with Prader-Willi and Angelman syndrome.

Prader-Willi (PWS) and Angelman (AS) syndromes are clinically distinct neurodevelopmental genetic diseases with multiple phenotypic manifestations. They are one of the most common genetic syndromes caused by non-Mendelian inheritance in the form of genomic imprinting, and can be attributable to the loss of gene expression due to imprinting within the chromosomal region 15q11-q13. Clinical diagnosis of PWS and AS is challenging, and the use of molecular and cytomolecular studies is recommended to help in determining the diagnosis of these conditions. The methylation analysis is a sensible approach; however there are several techniques for this purpose, such as the methylation-sensitive polymerase chain reaction (MS-PCR). This study aims to optimize the MS-PCR assay for the diagnosis of potential PWS and AS patients using DNA modified by sodium bisulfite. We used the MS-PCR technique of PCR described by Kosaki et al. (1997) adapted with betaine. All different concentrations of betaine used to amplify the methylated and unmethylated chromosomal region 15q11-q13 on the gene SNRPN showed amplification results, which increased proportionally to the concentration of betaine. The methylation analysis is a technically robust and reproducible screening method for PWS and AS. The MS-PCR assures a faster, cheaper and more efficient method for the primary diagnosis of the SNRPN gene in cases with PWS and AS, and may detect all of the three associated genetic abnormalities: deletion, uniparental disomy or imprinting errors.

Casos de leishmaniose visceral registrados no município de Montes Claros, Estado de Minas Gerais / Case of visceral leishmaniasis registered in the Montes Claros city,State of Minas Gerais

A leishmaniose visceral é uma zoonose típica de regiões tropicais. Há relatosem Minas Gerais desde 1940, sendo Montes Claros, atualmente um dos municípios de residência da doença, devido principalmente pelas parcas condições de vida da maioria dapopulação e pelas suas características climáticas. Com o objetivo de avaliar os aspectos epidemiológicos da leishmaniose em Montes Claros, foi feito um levantamento dos casos da doença no período de 2001 a 2007. Utilizaram-se dados referentes aos casos da leishmaniose visceral notificados no SINAN/SMS de Montes Claros durante esse período. Esta protozoose afetou principalmente faixas etárias compreendidas entre 1 a 4 anos e acima de 30 anos em ambos os sexos, sobretudo o sexo masculino. Tais dados significam que esse problema de saúde pública ainda não foi controlado nesse município, que pode ser considerado como exemplo do problema, pois é o município mais rico da região norte doEstado de Minas Gerais.

The visceral leishmaniasis is a zoonotic disease typical of tropical regions. There are reports in Minas Gerais since 1940, and Montes Claros, currently is thecity that occur this disease, mainly because the down living conditions of the majority of the population and its climatic features. The objective was to evaluate the epidemiological aspects of leishmaniasis in Montes Claros, was made a survey of cases of the disease in the period of 2001 to 2007. We used data on reported cases of visceral leishmaniasis in SINAN / SMS from Montes Claros during this period. This protozoiasis affect mainly ages rangingfrom 1 to 4 years and above 30 years for both sexes, especially males. These data mean that this public health problem has not yet been controlled in this city, which can be regarded asan example of this problem, because it is the richest city in the region north of the state of Minas Gerais.